Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
March-2025 Volume 31 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
March-2025 Volume 31 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Mitochondrial DNA copy number alterations: Key players in the complexity of glioblastoma (Review)

  • Authors:
    • Abdul Aziz Mohamed Yusoff
    • Siti Zulaikha Nashwa Mohd Khair
    • Siti Muslihah Abd Radzak
  • View Affiliations / Copyright

    Affiliations: Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
    Copyright: © Mohamed Yusoff et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 78
    |
    Published online on: January 24, 2025
       https://doi.org/10.3892/mmr.2025.13443
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Renowned as a highly invasive and lethal tumor derived from neural stem cells in the central nervous system, glioblastoma (GBM) exhibits substantial histopathological variation and genomic complexity, which drive its rapid progression and therapeutic resistance. Alterations in mitochondrial DNA (mtDNA) copy number (CN) serve a crucial role in GBM development and progression, affecting various aspects of tumor biology, including energy production, oxidative stress regulation and cellular adaptability. Fluctuations in mtDNA levels, whether elevated or diminished, can impair mitochondrial function, potentially disrupting oxidative phosphorylation and amplifying reactive oxygen species generation, thereby fueling tumor growth and influencing treatment responses. Understanding the mechanisms of mtDNA‑CN variations, and their interplay with genetic and environmental elements in the tumor microenvironment, is essential for advancing diagnostic and therapeutic strategies. Targeting mtDNA alterations could strengthen treatment efficacy, mitigate resistance and ultimately enhance the prognosis of patients with this aggressive brain tumor. The present review summarizes the existing literature on mtDNA alterations, specifically emphasizing variations in mtDNA‑CN and their association with GBM by surveying articles published between 1996 and 2024, sourced from databases such as Scopus, PubMed and Google Scholar. In addition, the review provides a brief overview of mitochondrial genome architecture, knowledge regarding the regulation of mtDNA integrity and CN, and how mitochondria significantly impact GBM tumorigenesis. This review further presents information on therapeutic approaches for restoring mtDNA‑CN that contribute to optimized mitochondrial function and improved health outcomes.
View Figures

Figure 1

View References

1 

Libby CJ, McConathy J, Darley-Usmar V and Hjelmeland AB: The role of metabolic plasticity in blood and brain stem cell pathophysiology. Cancer Res. 80:5–16. 2020. View Article : Google Scholar : PubMed/NCBI

2 

Morrison AJ: Cancer cell metabolism connects epigenetic modifications to transcriptional regulation. FEBS J. 289:1302–1314. 2022. View Article : Google Scholar : PubMed/NCBI

3 

Seker-Polat F, Pinarbasi Degirmenci N, Solaroglu I and Bagci-Onder T: Tumor cell infiltration into the brain in glioblastoma: From mechanisms to clinical perspectives. Cancers (Basel). 14:4432022. View Article : Google Scholar : PubMed/NCBI

4 

Pandey N, Anastasiadis P, Carney CP, Kanvinde PP, Woodworth GF, Winkles JA and Kim AJ: Nanotherapeutic treatment of the invasive glioblastoma tumor microenvironment. Adv Drug Deliv Rev. 188:1144152022. View Article : Google Scholar : PubMed/NCBI

5 

Obrador E, Moreno-Murciano P, Oriol-Caballo M, López-Blanch R, Pineda B, Gutiérrez-Arroyo JL, Loras A, Gonzalez-Bonet LG, Martinez-Cadenas C, Estrela JM and Marqués-Torrejón MÁ: Glioblastoma therapy: Past, present and future. Int J Mol Sci. 25:25292024. View Article : Google Scholar : PubMed/NCBI

6 

San-Millán I: The key role of mitochondrial function in health and disease. Antioxidants (Basel). 12:7822023. View Article : Google Scholar : PubMed/NCBI

7 

Wang SF, Tseng LM and Lee HC: Role of mitochondrial alterations in human cancer progression and cancer immunity. J Biomed Sci. 30:612023. View Article : Google Scholar : PubMed/NCBI

8 

Leão Barros MB, Pinheiro DDR and Borges BDN: Mitochondrial DNA alterations in glioblastoma (GBM). Int J Mol Sci. 22:58552021. View Article : Google Scholar : PubMed/NCBI

9 

Mohamed Yusoff AA: Role of mitochondrial DNA mutations in brain tumors: A mini-review. J Cancer Res Ther. 11:535–544. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Abd Radzak SM, Mohd Khair SZN, Ahmad F, Patar A, Idris Z and Mohamed Yusoff AA: Insights regarding mitochondrial DNA copy number alterations in human cancer (Review). Int J Mol Med. 50:1042022. View Article : Google Scholar : PubMed/NCBI

11 

Denisenko TV, Gorbunova AS and Zhivotovsky B: Mitochondrial involvement in migration, invasion and metastasis. Front Cell Dev Biol. 7:3552019. View Article : Google Scholar : PubMed/NCBI

12 

Zhang Z, Yang D, Zhou B, Luan Y, Yao Q, Liu Y, Yang S, Jia J, Xu Y, Bie X, et al: Decrease of MtDNA copy number affects mitochondrial function and involves in the pathological consequences of ischaemic stroke. J Cell Mol Med. 26:4157–4168. 2022. View Article : Google Scholar : PubMed/NCBI

13 

Tuchalska-Czuroń J, Lenart J, Augustyniak J and Durlik M: Is mitochondrial DNA copy number a good prognostic marker in resectable pancreatic cancer? Pancreatology. 19:73–79. 2019. View Article : Google Scholar : PubMed/NCBI

14 

Lin Y, Yang B, Huang Y, Zhang Y, Jiang Y, Ma L and Shen YQ: Mitochondrial DNA-targeted therapy: A novel approach to combat cancer. Cell Insight. 2:1001132023. View Article : Google Scholar : PubMed/NCBI

15 

Schaff LR and Mellinghoff IK: Glioblastoma and other primary brain malignancies in adults: A review. JAMA. 329:574–587. 2023. View Article : Google Scholar : PubMed/NCBI

16 

Ostrom QT, Price M, Neff C, Cioffi G, Waite KA, Kruchko C and Barnholtz-Sloan JS: CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2016–2020. Neuro Oncol. 25 (12 Suppl 2):iv1–iv99. 2023. View Article : Google Scholar : PubMed/NCBI

17 

Thomas DL: 2021 Updates to the World Health Organization classification of adult-type and pediatric-type diffuse gliomas: A clinical practice review. Chin Clin Oncol. 12:72023. View Article : Google Scholar : PubMed/NCBI

18 

Zhang P, Xia Q, Liu L, Li S and Dong L: Current opinion on molecular characterization for GBM classification in guiding clinical diagnosis, prognosis, and therapy. Front Mol Biosci. 7:5627982020. View Article : Google Scholar : PubMed/NCBI

19 

Grochans S, Cybulska AM, Simińska D, Korbecki J, Kojder K, Chlubek D and Baranowska-Bosiacka I: Epidemiology of glioblastoma multiforme-literature review. Cancers (Basel). 14:24122022. View Article : Google Scholar : PubMed/NCBI

20 

Ostrom QT, Price M, Neff C, Cioffi G, Waite KA, Kruchko C and Barnholtz-Sloan JS: CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the United States in 2015–2019. Neuro Oncol. 24 (Suppl 5):v1–v95. 2022. View Article : Google Scholar : PubMed/NCBI

21 

Siegel RL, Giaquinto AN and Jemal A: Cancer statistics, 2024. CA Cancer J Clin. 74:12–49. 2024. View Article : Google Scholar : PubMed/NCBI

22 

Onciul R, Brehar FM, Toader C, Covache-Busuioc RA, Glavan LA, Bratu BG, Costin HP, Dumitrascu DI, Serban M and Ciurea AV: Deciphering glioblastoma: Fundamental and novel insights into the biology and therapeutic strategies of gliomas. Curr Issues Mol Biol. 46:2402–2443. 2024. View Article : Google Scholar : PubMed/NCBI

23 

Tan AC, Ashley DM, López GY, Malinzak M, Friedman HS and Khasraw M: Management of glioblastoma: State of the art and future directions. CA Cancer J Clin. 70:299–312. 2020. View Article : Google Scholar : PubMed/NCBI

24 

Yalamarty SSK, Filipczak N, Li X, Subhan MA, Parveen F, Ataide JA, Rajmalani BA and Torchilin VP: Mechanisms of resistance and current treatment options for glioblastoma multiforme (GBM). Cancers (Basel). 15:21162023. View Article : Google Scholar : PubMed/NCBI

25 

Ohka F, Natsume A and Wakabayashi T: Current trends in targeted therapies for glioblastoma multiforme. Neurol Res Int. 2012:8784252012. View Article : Google Scholar : PubMed/NCBI

26 

Ohgaki H and Kleihues P: The definition of primary and secondary glioblastoma. Clin Cancer Res. 19:764–772. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P and Ellison DW: The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathol. 131:803–820. 2016. View Article : Google Scholar : PubMed/NCBI

28 

Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, et al: The 2021 WHO Classification of tumors of the central nervous system: A summary. Neuro Oncol. 23:1231–1251. 2021. View Article : Google Scholar : PubMed/NCBI

29 

Torrisi F, Alberghina C, D'Aprile S, Pavone AM, Longhitano L, Giallongo S, Tibullo D, Di Rosa M, Zappalà A, Cammarata FP, et al: The hallmarks of glioblastoma: Heterogeneity, intercellular crosstalk and molecular signature of invasiveness and progression. Biomedicines. 10:8062022. View Article : Google Scholar : PubMed/NCBI

30 

Cancer Genome Atlas Research Network, . Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 455:1061–1068. 2008. View Article : Google Scholar : PubMed/NCBI

31 

Verdugo E, Puerto I and Medina MÁ: An update on the molecular biology of glioblastoma, with clinical implications and progress in its treatment. Cancer Commun (Lond). 42:1083–1111. 2022. View Article : Google Scholar : PubMed/NCBI

32 

Marker DF, Agnihotri S, Amankulor N, Murdoch GH and Pearce TM: The dominant TP53 hotspot mutation in IDH-mutant astrocytoma, R273C, has distinctive pathologic features and sex-specific prognostic implications. Neurooncol Adv. 4:vdab1822021.PubMed/NCBI

33 

Dekker LJM, Verheul C, Wensveen N, Leenders W, Lamfers MLM, Leenstra S and Luider TM: Effects of the IDH1 R132H mutation on the energy metabolism: A comparison between tissue and corresponding primary glioma cell cultures. ACS Omega. 7:3568–3578. 2022. View Article : Google Scholar : PubMed/NCBI

34 

Lan Z, Li X and Zhang X Glioblastoma: An update in pathology, molecular mechanisms and biomarkers. Int J Mol Sci. 25:30402024. View Article : Google Scholar : PubMed/NCBI

35 

Mohd Khair SZN, Abd Radzak SM and Mohamed Yusoff AA: The uprising of mitochondrial DNA biomarker in cancer. Dis Markers. 2021:76752692021. View Article : Google Scholar : PubMed/NCBI

36 

Jacobs LJHC and Riemer J: Maintenance of small molecule redox homeostasis in mitochondria. FEBS Lett. 597:205–223. 2023. View Article : Google Scholar : PubMed/NCBI

37 

Nguyen TT, Wei S, Nguyen TH, Jo Y, Zhang Y, Park W, Gariani K, Oh CM, Kim HH, Ha KT, et al: Mitochondria-associated programmed cell death as a therapeutic target for age-related disease. Exp Mol Med. 55:1595–1619. 2023. View Article : Google Scholar : PubMed/NCBI

38 

Antonucci S, Di Lisa F and Kaludercic N: Mitochondrial reactive oxygen species in physiology and disease. Cell Calcium. 94:1023442021. View Article : Google Scholar : PubMed/NCBI

39 

Habbane M, Montoya J, Rhouda T, Sbaoui Y, Radallah D and Emperador S: Human mitochondrial DNA: Particularities and diseases. Biomedicines. 9:13642021. View Article : Google Scholar : PubMed/NCBI

40 

Bonekamp NA and Larsson NG: SnapShot: Mitochondrial nucleoid. Cell. 172:388–388.e1. 2018. View Article : Google Scholar : PubMed/NCBI

41 

Brown TA, Tkachuk AN, Shtengel G, Kopek BG, Bogenhagen DF, Hess HF and Clayton DA: Superresolution fluorescence imaging of mitochondrial nucleoids reveals their spatial range, limits, and membrane interaction. Mol Cell Biol. 31:4994–5010. 2011. View Article : Google Scholar : PubMed/NCBI

42 

Kukat C, Wurm CA, Spåhr H, Falkenberg M, Larsson NG and Jakobs S: Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA. Proc Natl Acad Sci USA. 108:13534–13539. 2011. View Article : Google Scholar : PubMed/NCBI

43 

He J, Cooper HM, Reyes A, Di Re M, Sembongi H, Litwin TR, Gao J, Neuman KC, Fearnley IM, Spinazzola A, et al: Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis. Nucleic Acids Res. 40:6109–6121. 2012. View Article : Google Scholar : PubMed/NCBI

44 

Han S, Udeshi ND, Deerinck TJ, Svinkina T, Ellisman MH, Carr SA and Ting AY: Proximity biotinylation as a method for mapping proteins associated with mtDNA in living cells. Cell Chem Biol. 24:404–414. 2017. View Article : Google Scholar : PubMed/NCBI

45 

Alam TI, Kanki T, Muta T, Ukaji K, Abe Y, Nakayama H, Takio K, Hamasaki N and Kang D: Human mitochondrial DNA is packaged with TFAM. Nucleic Acids Res. 31:1640–1645. 2003. View Article : Google Scholar : PubMed/NCBI

46 

Wang YE, Marinov GK, Wold BJ and Chan DC: Genome-wide analysis reveals coating of the mitochondrial genome by TFAM. PLoS One. 8:e745132013. View Article : Google Scholar : PubMed/NCBI

47 

Ngo HB, Lovely GA, Phillips R and Chan DC: Distinct structural features of TFAM drive mitochondrial DNA packaging versus transcriptional activation. Nat Commun. 5:30772014. View Article : Google Scholar : PubMed/NCBI

48 

Farge G, Mehmedovic M, Baclayon M, van den Wildenberg SMJL, Roos WH, Gustafsson CM, Wuite GJ and Falkenberg M: In vitro-reconstituted nucleoids can block mitochondrial DNA replication and transcription. Cell Rep. 8:66–74. 2014. View Article : Google Scholar : PubMed/NCBI

49 

Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, et al: Sequence and organization of the human mitochondrial genome. Nature. 290:457–465. 1981. View Article : Google Scholar : PubMed/NCBI

50 

Slone J and Huang T: The special considerations of gene therapy for mitochondrial diseases. NPJ Genom Med. 5:72020. View Article : Google Scholar : PubMed/NCBI

51 

Basu U, Bostwick AM, Das K, Dittenhafer-Reed KE and Patel SS: Structure, mechanism, and regulation of mitochondrial DNA transcription initiation. J Biol Chem. 295:18406–18425. 2020. View Article : Google Scholar : PubMed/NCBI

52 

Ren B, Guan MX, Zhou T, Cai X and Shan G: Emerging functions of mitochondria-encoded noncoding RNAs. Trends Genet. 39:125–139. 2023. View Article : Google Scholar : PubMed/NCBI

53 

Montoya J, Christianson T, Levens D, Rabinowitz M and Attardi G: Identification of initiation sites for heavy-strand and light-strand transcription in human mitochondrial DNA. Proc Natl Acad Sci USA. 79:7195–7199. 1982. View Article : Google Scholar : PubMed/NCBI

54 

Zollo O, Tiranti V and Sondheimer N: Transcriptional requirements of the distal heavy-strand promoter of mtDNA. Proc Natl Acad Sci USA. 109:6508–6512. 2012. View Article : Google Scholar : PubMed/NCBI

55 

Tan BG, Gustafsson CM and Falkenberg M: Mechanisms and regulation of human mitochondrial transcription. Nat Rev Mol Cell Biol. 25:119–132. 2024. View Article : Google Scholar : PubMed/NCBI

56 

Yan B, Tzertzinis G, Schildkraut I and Ettwiller L: Comprehensive determination of transcription start sites derived from all RNA polymerases using ReCappable-seq. Genome Res. 32:162–174. 2022. View Article : Google Scholar : PubMed/NCBI

57 

Tan BG, Mutti CD, Shi Y, Xie X, Zhu X, Silva-Pinheiro P, Menger KE, Díaz-Maldonado H, Wei W, Nicholls TJ, et al: The human mitochondrial genome contains a second light strand promoter. Mol Cell. 82:3646–3660.e9. 2022. View Article : Google Scholar : PubMed/NCBI

58 

Kummer E and Ban N: Mechanisms and regulation of protein synthesis in mitochondria. Nat Rev Mol Cell Biol. 22:307–325. 2021. View Article : Google Scholar : PubMed/NCBI

59 

Menger KE, Rodríguez-Luis A, Chapman J and Nicholls TJ: Controlling the topology of mammalian mitochondrial DNA. Open Biol. 11:2101682021. View Article : Google Scholar : PubMed/NCBI

60 

Matkarimov BT and Saparbaev MK: DNA repair and mutagenesis in vertebrate mitochondria: Evidence for asymmetric DNA strand inheritance. Adv Exp Med Biol. 1241:77–100. 2020. View Article : Google Scholar : PubMed/NCBI

61 

Falkenberg M, Larsson NG and Gustafsson CM: Replication and transcription of human mitochondrial DNA. Annu Rev Biochem. 93:47–77. 2024. View Article : Google Scholar : PubMed/NCBI

62 

Liu Y, Liu H, Zhang F and Xu H: The initiation of mitochondrial DNA replication. Biochem Soc Trans. 52:1243–1251. 2024. View Article : Google Scholar : PubMed/NCBI

63 

Falkenberg M: Mitochondrial DNA replication in mammalian cells: Overview of the pathway. Essays Biochem. 62:287–296. 2018. View Article : Google Scholar : PubMed/NCBI

64 

Peter B and Falkenberg M: TWINKLE and other human mitochondrial DNA helicases: Structure, function and disease. Genes (Basel). 11:4082020. View Article : Google Scholar : PubMed/NCBI

65 

Silva-Pinheiro P, Pardo-Hernández C, Reyes A, Tilokani L, Mishra A, Cerutti R, Li S, Rozsivalova DH, Valenzuela S, Dogan SA, et al: DNA polymerase gamma mutations that impair holoenzyme stability cause catalytic subunit depletion. Nucleic Acids Res. 49:5230–5248. 2021. View Article : Google Scholar : PubMed/NCBI

66 

Posse V, Al-Behadili A, Uhler JP, Clausen AR, Reyes A, Zeviani M, Falkenberg M and Gustafsson CM: RNase H1 directs origin-specific initiation of DNA replication in human mitochondria. PLoS Genet. 15:e10077812019. View Article : Google Scholar : PubMed/NCBI

67 

Fusté JM, Wanrooij S, Jemt E, Granycome CE, Cluett TJ, Shi Y, Atanassova N, Holt IJ, Gustafsson CM and Falkenberg M: Mitochondrial RNA polymerase is needed for activation of the origin of light-strand DNA replication. Mol Cell. 37:67–78. 2010. View Article : Google Scholar : PubMed/NCBI

68 

Sarfallah A, Zamudio-Ochoa A, Anikin M and Temiakov D: Mechanism of transcription initiation and primer generation at the mitochondrial replication origin OriL. EMBO J. 40:e1079882021. View Article : Google Scholar : PubMed/NCBI

69 

Picard M: Blood mitochondrial DNA copy number: What are we counting? Mitochondrion. 60:1–11. 2021. View Article : Google Scholar : PubMed/NCBI

70 

Kozhukhar N, Fant A and Alexeyev MF: Quantification of mtDNA content in cultured cells by direct droplet digital PCR. Mitochondrion. 61:102–113. 2021. View Article : Google Scholar : PubMed/NCBI

71 

Castellani CA, Longchamps RJ, Sun J, Guallar E and Arking DE: Thinking outside the nucleus: Mitochondrial DNA copy number in health and disease. Mitochondrion. 53:214–223. 2020. View Article : Google Scholar : PubMed/NCBI

72 

Koller A, Filosi M, Weissensteiner H, Fazzini F, Gorski M, Pattaro C, Schönherr S, Forer L, Herold JM, Stark KJ, et al: Nuclear and mitochondrial genetic variants associated with mitochondrial DNA copy number. Sci Rep. 14:20832024. View Article : Google Scholar : PubMed/NCBI

73 

Rath SP, Gupta R, Todres E, Wang H, Jourdain AA, Ardlie KG, Calvo SE and Mootha VK: Mitochondrial genome copy number variation across tissues in mice and humans. Proc Natl Acad Sci USA. 121:e24022911212024. View Article : Google Scholar

74 

Shokolenko I and Alexeyev M: Mitochondrial DNA: Consensuses and controversies. DNA (Basel). 2:131–148. 2022.PubMed/NCBI

75 

Khozhukhar N, Spadafora D, Rodriguez Y and Alexeyev M: Elimination of mitochondrial DNA from mammalian cells. Curr Protoc Cell Biol. 78:20.11.1–20.11.14. 2018. View Article : Google Scholar : PubMed/NCBI

76 

O'Hara R, Tedone E, Ludlow A, Huang E, Arosio B, Mari D and Shay JW: Quantitative mitochondrial DNA copy number determination using droplet digital PCR with single-cell resolution. Genome Res. 29:1878–1888. 2019. View Article : Google Scholar : PubMed/NCBI

77 

Matsushima Y, Matsumura K, Ishii S, Inagaki H, Suzuki T, Matsuda Y, Beck K and Kitagawa Y: Functional domains of chicken mitochondrial transcription factor A for the maintenance of mitochondrial DNA copy number in lymphoma cell line DT40. J Biol Chem. 278:31149–31158. 2003. View Article : Google Scholar : PubMed/NCBI

78 

Ekstrand MI, Falkenberg M, Rantanen A, Park CB, Gaspari M, Hultenby K, Rustin P, Gustafsson CM and Larsson NG: Mitochondrial transcription factor A regulates mtDNA copy number in mammals. Hum Mol Genet. 13:935–944. 2004. View Article : Google Scholar : PubMed/NCBI

79 

Kanki T, Ohgaki K, Gaspari M, Gustafsson CM, Fukuoh A, Sasaki N, Hamasaki N and Kang D: Architectural role of mitochondrial transcription factor A in maintenance of human mitochondrial DNA. Mol Cell Biol. 24:9823–9834. 2004. View Article : Google Scholar : PubMed/NCBI

80 

Bonekamp NA, Jiang M, Motori E, Garcia Villegas R, Koolmeister C, Atanassov I, Mesaros A, Park CB and Larsson NG: High levels of TFAM repress mammalian mitochondrial DNA transcription in vivo. Life Sci Alliance. 4:e2021010342021. View Article : Google Scholar : PubMed/NCBI

81 

Matsushima Y, Goto Y and Kaguni LS: Mitochondrial Lon protease regulates mitochondrial DNA copy number and transcription by selective degradation of mitochondrial transcription factor A (TFAM). Proc Natl Acad Sci USA. 107:18410–18415. 2010. View Article : Google Scholar : PubMed/NCBI

82 

Aasumets K, Basikhina Y, Pohjoismäki JL, Goffart S and Gerhold J: TFAM knockdown-triggered mtDNA-nucleoid aggregation and a decrease in mtDNA copy number induce the reorganization of nucleoid populations and mitochondria-associated ER-membrane contacts. Biochem Biophys Rep. 28:1011422021.PubMed/NCBI

83 

Matsuda T, Kanki T, Tanimura T, Kang D and Matsuura ET: Effects of overexpression of mitochondrial transcription factor A on lifespan and oxidative stress response in Drosophila melanogaster. Biochem Biophys Res Commun. 430:717–721. 2013. View Article : Google Scholar : PubMed/NCBI

84 

Maniura-Weber K, Goffart S, Garstka HL, Montoya J and Wiesner RJ: Transient overexpression of mitochondrial transcription factor A (TFAM) is sufficient to stimulate mitochondrial DNA transcription, but not sufficient to increase mtDNA copy number in cultured cells. Nucleic Acids Res. 32:6015–6027. 2004. View Article : Google Scholar : PubMed/NCBI

85 

Brinckmann A, Weiss C, Wilbert F, von Moers A, Zwirner A, Stoltenburg-Didinger G, Wilichowski E and Schuelke M: Regionalized pathology correlates with augmentation of mtDNA copy numbers in a patient with myoclonic epilepsy with ragged-red fibers (MERRF-syndrome). PLoS One. 5:e135132010. View Article : Google Scholar : PubMed/NCBI

86 

Kozhukhar N and Alexeyev MF: Limited predictive value of TFAM in mitochondrial biogenesis. Mitochondrion. 49:156–165. 2019. View Article : Google Scholar : PubMed/NCBI

87 

Lu B, Lee J, Nie X, Li M, Morozov YI, Venkatesh S, Bogenhagen DF, Temiakov D and Suzuki CK: Phosphorylation of human TFAM in mitochondria impairs DNA binding and promotes degradation by the AAA+ Lon protease. Mol Cell. 49:121–132. 2013. View Article : Google Scholar : PubMed/NCBI

88 

Kühl I, Miranda M, Posse V, Milenkovic D, Mourier A, Siira SJ, Bonekamp NA, Neumann U, Filipovska A, Polosa PL, et al: POLRMT regulates the switch between replication primer formation and gene expression of mammalian mtDNA. Sci Adv. 2:e16009632016. View Article : Google Scholar : PubMed/NCBI

89 

Sitarz KS, Yu-Wai-Man P, Pyle A, Stewart JD, Rautenstrauss B, Seeman P, Reilly MM, Horvath R and Chinnery PF: MFN2 mutations cause compensatory mitochondrial DNA proliferation. Brain. 135:e2191–3. –e220. 1–3. 2012. View Article : Google Scholar : PubMed/NCBI

90 

Vielhaber S, Debska-Vielhaber G, Peeva V, Schoeler S, Kudin AP, Minin I, Schreiber S, Dengler R, Kollewe K, Zuschratter W, et al: Mitofusin 2 mutations affect mitochondrial function by mitochondrial DNA depletion. Acta Neuropathol. 125:245–256. 2013. View Article : Google Scholar : PubMed/NCBI

91 

van Leeuwen N, Beekman M, Deelen J, van den Akker EB, de Craen AJM, Slagboom PE and 't Hart LM: Low mitochondrial DNA content associates with familial longevity: The leiden longevity study. Age (Dordr). 36:96292014. View Article : Google Scholar : PubMed/NCBI

92 

Mengel-From J, Thinggaard M, Dalgård C, Kyvik KO, Christensen K and Christiansen L: Mitochondrial DNA copy number in peripheral blood cells declines with age and is associated with general health among elderly. Hum Genet. 133:1149–1159. 2014. View Article : Google Scholar : PubMed/NCBI

93 

Mizuno G, Yamada H, Tsuboi Y, Munetsuna E, Yamazaki M, Ando Y, Kageyama I, Nouchi Y, Teshigawara A, Hattori Y, et al: Low mitochondrial DNA copy number in peripheral blood mononuclear cells is associated with future mortality risk: A long-term follow-up study from Japan. J Nutr Health Aging. 28:1000132024. View Article : Google Scholar : PubMed/NCBI

94 

Wang R, Lei H, Wang H, Qi L, Liu Y, Liu Y, Shi Y, Chen J and Shen QT: Dysregulated inter-mitochondrial crosstalk in glioblastoma cells revealed by in situ cryo-electron tomography. Proc Natl Acad Sci USA. 121:e23111601212024. View Article : Google Scholar : PubMed/NCBI

95 

Yuan Y, Ju YS, Kim Y, Li J, Wang Y, Yoon CJ, Yang Y, Martincorena I, Creighton CJ, Weinstein JN, et al: Comprehensive molecular characterization of mitochondrial genomes in human cancers. Nat Genet. 52:342–352. 2020. View Article : Google Scholar : PubMed/NCBI

96 

Watson DC, Bayik D, Storevik S, Moreino SS, Sprowls SA, Han J, Augustsson MT, Lauko A, Sravya P, Røsland GV, et al: GAP43-dependent mitochondria transfer from astrocytes enhances glioblastoma tumorigenicity. Nat Cancer. 4:648–664. 2023. View Article : Google Scholar : PubMed/NCBI

97 

Vidone M, Clima R, Santorsola M, Calabrese C, Girolimetti G, Kurelac I, Amato LB, Iommarini L, Trevisan E, Leone M, et al: A comprehensive characterization of mitochondrial DNA mutations in glioblastoma multiforme. Int J Biochem Cell Biol. 63:46–54. 2015. View Article : Google Scholar : PubMed/NCBI

98 

Mohamed Yusoff AA, Mohd Nasir KN, Haris K, Mohd Khair SZN, Abdul Ghani ARI, Idris Z and Abdullah JM: Detection of somatic mutations in the mitochondrial DNA control region D-loop in brain tumors: The first report in Malaysian patients. Oncol Lett. 14:5179–5188. 2017.PubMed/NCBI

99 

Radzak S, Khair Z, Ahmad F, Idris Z and Yusoff A: Accumulation of mitochondrial DNA microsatellite instability in Malaysian patients with primary central nervous system tumors. Turk Neurosurg. 31:99–106. 2021.PubMed/NCBI

100 

Yeung KY, Dickinson A, Donoghue JF, Polekhina G, White SJ, Grammatopoulos DK, McKenzie M, Johns TG and St John JC: The identification of mitochondrial DNA variants in glioblastoma multiforme. Acta Neuropathol Commun. 2:12014. View Article : Google Scholar : PubMed/NCBI

101 

Khair SZNM, Ab Radzak SM, Idris Z, Zin AAM, Ahmad WMAW and Yusoff AAM: The effect of somatic mutations in mitochondrial DNA on the survival of patients with primary brain tumors. Croat Med J. 65:111–121. 2024. View Article : Google Scholar : PubMed/NCBI

102 

Mohamed Yusoff AA, Zulfakhar FN, Mohd Khair SZN, Wan Abdullah WS, Abdullah JM and Idris Z: Mitochondrial 10398A>G NADH-dehydrogenase subunit 3 of complex I is frequently altered in intra-axial brain tumors in Malaysia. Brain Tumor Res Treat. 6:31–38. 2018. View Article : Google Scholar : PubMed/NCBI

103 

Lloyd RE, Keatley K, Littlewood DT, Meunier B, Holt WV, An Q, Higgins SC, Polyzoidis S, Stephenson KF, Ashkan K, et al: Identification and functional prediction of mitochondrial complex III and IV mutations associated with glioblastoma. Neuro Oncol. 17:942–952. 2015. View Article : Google Scholar : PubMed/NCBI

104 

Keatley K, Stromei-Cleroux S, Wiltshire T, Rajala N, Burton G, Holt WV, Littlewood DTJ, Briscoe AG, Jung J, Ashkan K, et al: Integrated approach reveals role of mitochondrial germ-line mutation F18L in Respiratory Chain, oxidative alterations, drug sensitivity, and patient prognosis in glioblastoma. Int J Mol Sci. 20:33642019. View Article : Google Scholar : PubMed/NCBI

105 

Mohamed Yusoff AA, Mohd Khair SZN, Abd Radzak SM, Idris Z and Lee HC: Prevalence of mitochondrial DNA common deletion in patients with gliomas and meningiomas: A first report from a Malaysian study group. J Chin Med Assoc. 83:838–844. 2020. View Article : Google Scholar : PubMed/NCBI

106 

Wang J, Qiu X, Huang J, Zhuo Z, Chen H, Zeng R, Wu H, Guo K, Yang Q, Ye H, et al: Development and validation of a novel mitophagy-related gene prognostic signature for glioblastoma multiforme. BMC Cancer. 22:6442022. View Article : Google Scholar : PubMed/NCBI

107 

Xie Z, Hua W and Wang H: Comprehensive analysis of mitochondrial dynamic-related genes on their functions and prognostic values for glioblastoma multiforme. Genes Dis. 11:1010842023. View Article : Google Scholar : PubMed/NCBI

108 

Su J and Li Y, Liu Q, Peng G, Qin C and Li Y: Identification of SSBP1 as a ferroptosis-related biomarker of glioblastoma based on a novel mitochondria-related gene risk model and in vitro experiments. J Transl Med. 20:4402022. View Article : Google Scholar : PubMed/NCBI

109 

Peng G, Feng Y, Wang X, Huang W and Li Y: The mitochondria-related gene risk mode revealed p66Shc as a prognostic mitochondria-related gene of glioblastoma. Sci Rep. 14:114182024. View Article : Google Scholar : PubMed/NCBI

110 

Porporato PE, Filigheddu N, Pedro JMB, Kroemer G and Galluzzi L: Mitochondrial metabolism and cancer. Cell Res. 28:265–280. 2018. View Article : Google Scholar : PubMed/NCBI

111 

Raimondi V, Ciccarese F and Ciminale V: Oncogenic pathways and the electron transport chain: A dangeROS liaison. Br J Cancer. 122:168–181. 2020. View Article : Google Scholar : PubMed/NCBI

112 

Franceschi S, Corsinovi D, Lessi F, Tantillo E, Aretini P, Menicagli M, Scopelliti C, Civita P, Pasqualetti F, Naccarato AG, et al: Mitochondrial enzyme GLUD2 plays a critical role in glioblastoma progression. EBioMedicine. 37:56–67. 2018. View Article : Google Scholar : PubMed/NCBI

113 

Li C, Peng W, Song X, Wang Q and Wang W: Anticancer effect of icaritin inhibits cell growth of colon cancer through reactive oxygen species, Bcl-2 and cyclin D1/E signaling. Oncol Lett. 12:3537–3542. 2016. View Article : Google Scholar : PubMed/NCBI

114 

Wang X, Liu J, Jiang L, Wei X, Niu C, Wang R, Zhang J, Meng D and Yao K: Bach1 induces endothelial cell apoptosis and cell-cycle arrest through ROS generation. Oxid Med Cell Longev. 2016:62340432016. View Article : Google Scholar : PubMed/NCBI

115 

Zhao J, Ma X, Gao P, Han X, Zhao P, Xie F and Liu M: Advancing glioblastoma treatment by targeting metabolism. Neoplasia. 51:1009852024. View Article : Google Scholar : PubMed/NCBI

116 

Zhang R, Wang C, Zheng X, Li S, Zhang W, Kang Z, Yin S, Chen J, Chen F and Li W: Warburg effect-related risk scoring model to assess clinical significance and immunity characteristics of glioblastoma. Cancer Med. 12:20639–20654. 2023. View Article : Google Scholar : PubMed/NCBI

117 

Chisari A, Golán I, Campisano S, Gélabert C, Moustakas A, Sancho P and Caja L: Glucose and amino acid metabolic dependencies linked to stemness and metastasis in different aggressive cancer types. Front Pharmacol. 12:7237982021. View Article : Google Scholar : PubMed/NCBI

118 

Iranmanesh Y, Jiang B, Favour OC, Dou Z, Wu J, Li J and Sun C: Mitochondria's role in the maintenance of cancer stem cells in glioblastoma. Front Oncol. 11:5826942021. View Article : Google Scholar : PubMed/NCBI

119 

Nakhle J, Khattar K, Özkan T, Boughlita A, Abba Moussa D, Darlix A, Lorcy F, Rigau V, Bauchet L, Gerbal-Chaloin S, et al: Mitochondria transfer from mesenchymal stem cells confers chemoresistance to glioblastoma stem cells through metabolic rewiring. Cancer Res Commun. 3:1041–1056. 2023. View Article : Google Scholar : PubMed/NCBI

120 

Qian W and Van Houten B: Alterations in bioenergetics due to changes in mitochondrial DNA copy number. Methods. 51:452–457. 2010. View Article : Google Scholar : PubMed/NCBI

121 

Singh KK, Ayyasamy V, Owens KM, Koul MS and Vujcic M: Mutations in mitochondrial DNA polymerase-gamma promote breast tumorigenesis. J Hum Genet. 54:516–524. 2009. View Article : Google Scholar : PubMed/NCBI

122 

Dickinson A, Yeung KY, Donoghue J, Baker MJ, Kelly RD, McKenzie M, Johns TG and St John JC: The regulation of mitochondrial DNA copy number in glioblastoma cells. Cell Death Differ. 20:1644–1653. 2013. View Article : Google Scholar : PubMed/NCBI

123 

Shen H, Yu M, Tsoli M, Chang C, Joshi S, Liu J, Ryall S, Chornenkyy Y, Siddaway R, Hawkins C and Ziegler DS: Targeting reduced mitochondrial DNA quantity as a therapeutic approach in pediatric high-grade gliomas. Neuro Oncol. 22:139–151. 2020. View Article : Google Scholar : PubMed/NCBI

124 

Ricci C, Pastukh V, Leonard J, Turrens J, Wilson G, Schaffer D and Schaffer SW: Mitochondrial DNA damage triggers mitochondrial-superoxide generation and apoptosis. Am J Physiol Cell Physiol. 294:C413–C422. 2008. View Article : Google Scholar : PubMed/NCBI

125 

Park JS, Sharma LK, Li H, Xiang R, Holstein D, Wu J, Lechleiter J, Naylor SL, Deng JJ, Lu J and Bai Y: A heteroplasmic, not homoplasmic, mitochondrial DNA mutation promotes tumorigenesis via alteration in reactive oxygen species generation and apoptosis. Hum Mol Genet. 18:1578–1589. 2009. View Article : Google Scholar : PubMed/NCBI

126 

Sadakierska-Chudy A, Kotarska A, Frankowska M, Jastrzębska J, Wydra K, Miszkiel J, Przegaliński E and Filip M: The alterations in mitochondrial DNA copy number and nuclear-encoded mitochondrial genes in rat brain structures after cocaine self-administration. Mol Neurobiol. 54:7460–7470. 2017. View Article : Google Scholar : PubMed/NCBI

127 

Hu L, Yao X and Shen Y: Altered mitochondrial DNA copy number contributes to human cancer risk: Evidence from an updated meta-analysis. Sci Rep. 6:358592016. View Article : Google Scholar : PubMed/NCBI

128 

Al-Kafaji G and Golbahar J: High glucose-induced oxidative stress increases the copy number of mitochondrial DNA in human mesangial cells. Biomed Res Int. 2013:7549462013. View Article : Google Scholar : PubMed/NCBI

129 

Long S, Zheng Y, Deng X, Guo J, Xu Z, Scharffetter-Kochanek K, Dou Y and Jiang M: Maintaining mitochondrial DNA copy number mitigates ROS-induced oocyte decline and female reproductive aging. Commun Biol. 7:12292024. View Article : Google Scholar : PubMed/NCBI

130 

Grady CI, Walsh LM and Heiss JD: Mitoepigenetics and gliomas: Epigenetic alterations to mitochondrial DNA and nuclear DNA alter mtDNA expression and contribute to glioma pathogenicity. Front Neurol. 14:11547532023. View Article : Google Scholar : PubMed/NCBI

131 

Liao S, Chen L, Song Z and He H: The fate of damaged mitochondrial DNA in the cell. Biochim Biophys Acta Mol Cell Res. 1869:1192332022. View Article : Google Scholar : PubMed/NCBI

132 

Fu Y, Tigano M and Sfeir A: Safeguarding mitochondrial genomes in higher eukaryotes. Nat Struct Mol Biol. 27:687–695. 2020. View Article : Google Scholar : PubMed/NCBI

133 

Lee HC and Wei YH: Mitochondrial role in life and death of the cell. J Biomed Sci. 7:2–15. 2000. View Article : Google Scholar : PubMed/NCBI

134 

Fontana GA and Gahlon HL: Mechanisms of replication and repair in mitochondrial DNA deletion formation. Nucleic Acids Res. 48:11244–11258. 2020. View Article : Google Scholar : PubMed/NCBI

135 

Reznik E, Miller ML, Şenbabaoğlu Y, Riaz N, Sarungbam J, Tickoo SK, Al-Ahmadie HA, Lee W, Seshan VE, Hakimi AA and Sander C: Mitochondrial DNA copy number variation across human cancers. Elife. 5:e107692016. View Article : Google Scholar : PubMed/NCBI

136 

Dardaud LM, Bris C, Desquiret-Dumas V, Boisselier B, Tabouret E, Mokhtari K, Figarella-Branger D, Rousseau A and Procaccio V: High mitochondrial DNA copy number is associated with longer survival in young patients with glioblastoma. Neuro Oncol. 21:1084–1085. 2019. View Article : Google Scholar : PubMed/NCBI

137 

Liang BC: Evidence for association of mitochondrial DNA sequence amplification and nuclear localization in human low-grade gliomas. Mutat Res. 354:27–33. 1996. View Article : Google Scholar : PubMed/NCBI

138 

Liang BC and Hays L: Mitochondrial DNA copy number changes in human gliomas. Cancer Lett. 105:167–173. 1996. View Article : Google Scholar : PubMed/NCBI

139 

Correia RL, Oba-Shinjo SM, Uno M, Huang N and Marie SKN: Mitochondrial DNA depletion and its correlation with TFAM, TFB1M, TFB2M and POLG in human diffusely infiltrating astrocytomas. Mitochondrion. 11:48–53. 2011. View Article : Google Scholar : PubMed/NCBI

140 

Soltész B, Pös O, Wlachovska Z, Budis J, Hekel R, Strieskova L, Liptak JB, Krampl W, Styk J, Németh N, et al: Mitochondrial DNA copy number changes, heteroplasmy, and mutations in plasma-derived exosomes and brain tissue of glioblastoma patients. Mol Cell Probes. 66:1018752022. View Article : Google Scholar : PubMed/NCBI

141 

Marucci G, Maresca A, Caporali L, Farnedi A, Betts CM, Morandi L, de Biase D, Cerasoli S, Foschini MP, Bonora E, et al: Oncocytic glioblastoma: A glioblastoma showing oncocytic changes and increased mitochondrial DNA copy number. Hum Pathol. 44:1867–1876. 2013. View Article : Google Scholar : PubMed/NCBI

142 

Zhang J, Li D, Qu F, Chen Y, Li G, Jiang H, Huang X, Yang H and Xing J: Association of leukocyte mitochondrial DNA content with glioma risk: Evidence from a Chinese case-control study. BMC Cancer. 14:6802014. View Article : Google Scholar : PubMed/NCBI

143 

Shen J, Song R, Lu Z and Zhao H: Mitochondrial DNA copy number in whole blood and glioma risk: A case control study. Mol Carcinog. 55:2089–2094. 2016. View Article : Google Scholar : PubMed/NCBI

144 

Zhang Y, Qu Y, Gao K, Yang Q, Shi B, Hou P and Ji M: High copy number of mitochondrial DNA (mtDNA) predicts good prognosis in glioma patients. Am J Cancer Res. 5:1207–1216. 2015.PubMed/NCBI

145 

Sourty B, Dardaud LM, Bris C, Desquiret-Dumas V, Boisselier B, Basset L, Figarella-Branger D, Morel A, Sanson M, Procaccio V and Rousseau A: Mitochondrial DNA copy number as a prognostic marker is age-dependent in adult glioblastoma. Neurooncol Adv. 4:vdab1912022.PubMed/NCBI

146 

Ab Radzak SM, Mohd Khair SZN, Idris Z, Wan Ahmad WMA, Patar A and Mohamed Yusoff AA: Mitochondrial deoxyribonucleic acid copy number elevation as a predictor for extended survival and favorable outcomes in high-grade brain tumor patients: A Malaysian study. Eurasian J Med. 56:7–14. 2024. View Article : Google Scholar : PubMed/NCBI

147 

Hua L, Juratli TA, Zhu H, Deng J, Wang D, Sun S, Xie Q, Wakimoto H and Gong Y: High tumor mitochondrial DNA content correlates with an improved patient's outcome in WHO grade III Meningioma. Front Oncol. 10:5422942020. View Article : Google Scholar : PubMed/NCBI

148 

Sravya P, Krishna ASU, Santosh V and Arivazhagan A: Mitochondrial DNA content in tumor tissue and blood of patients with glioblastoma-A reliable biomarker? Int J Neurooncol. 3:12–18. 2020. View Article : Google Scholar

149 

Sravya P, Nimbalkar VP, Kanuri NN, Sugur H, Verma BK, Kundu P, Rao S, Uday Krishna AS, Somanna S, Kondaiah P, et al: Low mitochondrial DNA copy number is associated with poor prognosis and treatment resistance in glioblastoma. Mitochondrion. 55:154–163. 2020. View Article : Google Scholar : PubMed/NCBI

150 

Chen Y, Zhang J, Huang X, Zhang J, Zhou X, Hu J, Li G, He S and Xing J: High leukocyte mitochondrial DNA content contributes to poor prognosis in glioma patients through its immunosuppressive effect. Br J Cancer. 113:99–106. 2015. View Article : Google Scholar : PubMed/NCBI

151 

Sun X and St John JC: Modulation of mitochondrial DNA copy number in a model of glioblastoma induces changes to DNA methylation and gene expression of the nuclear genome in tumours. Epigenetics Chromatin. 11:532018. View Article : Google Scholar : PubMed/NCBI

152 

Braun Y, Filipski K, Bernatz S, Baumgarten P, Roller B, Zinke J, Zeiner PS, Ilina E, Senft C, Ronellenfitsch MW, et al: Linking epigenetic signature and metabolic phenotype in IDH mutant and IDH wildtype diffuse glioma. Neuropathol Appl Neurobiol. 47:379–393. 2021. View Article : Google Scholar : PubMed/NCBI

153 

Oliva CR, Nozell SE, Diers A, McClugage SG III, Sarkaria JN, Markert JM, Darley-Usmar VM, Bailey SM, Gillespie GY, Landar A and Griguer CE: Acquisition of temozolomide chemoresistance in gliomas leads to remodeling of mitochondrial electron transport chain. J Biol Chem. 285:39759–39767. 2010. View Article : Google Scholar : PubMed/NCBI

154 

Luna B, Bhatia S, Yoo C, Felty Q, Sandberg DI, Duchowny M, Khatib Z, Miller I, Ragheb J, Prasanna J and Roy D: Proteomic and mitochondrial genomic analyses of pediatric brain tumors. Mol Neurobiol. 52:1341–1363. 2015. View Article : Google Scholar : PubMed/NCBI

155 

Longchamps RJ, Castellani CA, Yang SY, Newcomb CE, Sumpter JA, Lane J, Grove ML, Guallar E, Pankratz N, Taylor KD, et al: Evaluation of mitochondrial DNA copy number estimation techniques. PLoS One. 15:e02281662020. View Article : Google Scholar : PubMed/NCBI

156 

Filograna R, Mennuni M, Alsina D and Larsson NG: Mitochondrial DNA copy number in human disease: The more the better? FEBS Lett. 595:976–1002. 2021. View Article : Google Scholar : PubMed/NCBI

157 

Domazet B, Maclennan GT, Lopez-Beltran A, Montironi R and Cheng L: Laser capture microdissection in the genomic and proteomic era: Targeting the genetic basis of cancer. Int J Clin Exp Pathol. 1:475–488. 2008.PubMed/NCBI

158 

Kurdi M, Bamaga A, Alkhotani A, Alsharif T, Abdel-Hamid GA, Selim ME, Alsinani T, Albeshri A, Badahdah A, Basheikh M and Baeesa S: Mitochondrial DNA alterations in glioblastoma and current therapeutic targets. Front Biosci (Landmark Ed). 29:3672024. View Article : Google Scholar : PubMed/NCBI

159 

Chen J, Zheng Q, Hicks JL, Trabzonlu L, Ozbek B, Jones T, Vaghasia AM, Larman TC, Wang R, Markowski MC, et al: MYC-driven increases in mitochondrial DNA copy number occur early and persist throughout prostatic cancer progression. JCI Insight. 8:e1698682023. View Article : Google Scholar : PubMed/NCBI

160 

Mou JJ, Peng J, Shi YY, Li N, Wang Y, Ke Y, Zhou YF and Zhou FX: Mitochondrial DNA content reduction induces aerobic glycolysis and reversible resistance to drug-induced apoptosis in SW480 colorectal cancer cells. Biomed Pharmacother. 103:729–737. 2018. View Article : Google Scholar : PubMed/NCBI

161 

Devic S: Warburg effect-a consequence or the cause of carcinogenesis? J Cancer. 7:817–822. 2016. View Article : Google Scholar : PubMed/NCBI

162 

Dickinson A, Yeung V and St. John J: Abnormal regulation of mitochondrial DNA copy number in glioblastoma multiforme cancer stem cells. Biol Reprod. 87 (Suppl 1):S5982012. View Article : Google Scholar

163 

Wiese W, Barczuk J, Racinska O, Siwecka N, Rozpedek-Kaminska W, Slupianek A, Sierpinski R and Majsterek I: PI3K/Akt/mTOR signaling pathway in blood malignancies-new therapeutic possibilities. Cancers (Basel). 15:52972023. View Article : Google Scholar : PubMed/NCBI

164 

Tufail M, Jiang CH and Li N: Altered metabolism in cancer: Insights into energy pathways and therapeutic targets. Mol Cancer. 23:2032024. View Article : Google Scholar : PubMed/NCBI

165 

Filograna R, Koolmeister C, Upadhyay M, Pajak A, Clemente P, Wibom R, Simard ML, Wredenberg A, Freyer C, Stewart JB and Larsson NG: Modulation of mtDNA copy number ameliorates the pathological consequences of a heteroplasmic mtDNA mutation in the mouse. Sci Adv. 5:eaav98242019. View Article : Google Scholar : PubMed/NCBI

166 

Tian Q, Moore AZ, Oppong R, Ding J, Zampino M, Fishbein KW, Spencer RG and Ferrucci L: Mitochondrial DNA copy number and heteroplasmy load correlate with skeletal muscle oxidative capacity by P31 MR spectroscopy. Aging Cell. 20:e134872021. View Article : Google Scholar : PubMed/NCBI

167 

Ding Q, Qi Y and Tsang SY: Mitochondrial biogenesis, mitochondrial dynamics, and mitophagy in the maturation of cardiomyocytes. Cells. 10:24632021. View Article : Google Scholar : PubMed/NCBI

168 

Liu L, Li Y, Chen G and Chen Q: Crosstalk between mitochondrial biogenesis and mitophagy to maintain mitochondrial homeostasis. J Biomed Sci. 30:862023. View Article : Google Scholar : PubMed/NCBI

169 

Popov LD: Mitochondrial biogenesis: An update. J Cell Mol Med. 24:4892–4899. 2020. View Article : Google Scholar : PubMed/NCBI

170 

Wredenberg A, Wibom R, Wilhelmsson H, Graff C, Wiener HH, Burden SJ, Oldfors A, Westerblad H and Larsson NG: Increased mitochondrial mass in mitochondrial myopathy mice. Proc Natl Acad Sci USA. 99:15066–15071. 2002. View Article : Google Scholar : PubMed/NCBI

171 

Qian L, Zhu Y, Deng C, Liang Z, Chen J, Chen Y, Wang X, Liu Y, Tian Y and Yang Y: Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases. Signal Transduct Target Ther. 9:502024. View Article : Google Scholar : PubMed/NCBI

172 

Viscomi C, Bottani E, Civiletto G, Cerutti R, Moggio M, Fagiolari G, Schon EA, Lamperti C and Zeviani M: In vivo correction of COX deficiency by activation of the AMPK/PGC-1α axis. Cell Metab. 14:80–90. 2011. View Article : Google Scholar : PubMed/NCBI

173 

Dillon LM, Williams SL, Hida A, Peacock JD, Prolla TA, Lincoln J and Moraes CT: Increased mitochondrial biogenesis in muscle improves aging phenotypes in the mtDNA mutator mouse. Hum Mol Genet. 21:2288–2297. 2012. View Article : Google Scholar : PubMed/NCBI

174 

Giordano C, Iommarini L, Giordano L, Maresca A, Pisano A, Valentino ML, Caporali L, Liguori R, Deceglie S, Roberti M, et al: Efficient mitochondrial biogenesis drives incomplete penetrance in Leber's hereditary optic neuropathy. Brain. 137:335–353. 2014. View Article : Google Scholar : PubMed/NCBI

175 

Wu J, Li J, Feng B, Bi Z, Zhu G, Zhang Y and Li X: Activation of AMPK-PGC-1α pathway ameliorates peritoneal dialysis related peritoneal fibrosis in mice by enhancing mitochondrial biogenesis. Ren Fail. 44:1545–1557. 2022. View Article : Google Scholar : PubMed/NCBI

176 

Pirinen E, Auranen M, Khan NA, Brilhante V, Urho N, Pessia A, Hakkarainen A, Kuula J, Heinonen U, Schmidt MS, et al: Niacin cures systemic NAD+ deficiency and improves muscle performance in adult-onset mitochondrial myopathy. Cell Metab. 31:1078–1090.e5. 2020. View Article : Google Scholar : PubMed/NCBI

177 

Liu Y, Bai H, Guo F, Thai PN, Luo X, Zhang P, Yang C, Feng X, Zhu D, Guo J, et al: PGC-1α activator ZLN005 promotes maturation of cardiomyocytes derived from human embryonic stem cells. Aging (Albany NY). 12:7411–7430. 2020. View Article : Google Scholar : PubMed/NCBI

178 

Sun S, Jiang T, Duan N, Wu M, Yan C, Li Y, Cai M and Wang Q: Activation of CB1R-dependent PGC-1α is involved in the improved mitochondrial biogenesis induced by electroacupuncture pretreatment. Rejuvenation Res. 24:104–119. 2021. View Article : Google Scholar : PubMed/NCBI

179 

Nishiyama S, Shitara H, Nakada K, Ono T, Sato A, Suzuki H, Ogawa T, Masaki H, Hayashi J and Yonekawa H: Over-expression of Tfam improves the mitochondrial disease phenotypes in a mouse model system. Biochem Biophys Res Commun. 401:26–31. 2010. View Article : Google Scholar : PubMed/NCBI

180 

Jiang M, Kauppila TES, Motori E, Li X, Atanassov I, Folz-Donahue K, Bonekamp NA, Albarran-Gutierrez S, Stewart JB and Larsson NG: Increased total mtDNA copy number cures male infertility despite unaltered mtDNA mutation load. Cell Metab. 26:429–436.e4. 2017. View Article : Google Scholar : PubMed/NCBI

181 

Ikeuchi M, Matsusaka H, Kang D, Matsushima S, Ide T, Kubota T, Fujiwara T, Hamasaki N, Takeshita A, Sunagawa K and Tsutsui H: Overexpression of mitochondrial transcription factor a ameliorates mitochondrial deficiencies and cardiac failure after myocardial infarction. Circulation. 112:683–690. 2005. View Article : Google Scholar : PubMed/NCBI

182 

Hayashi Y, Yoshida M, Yamato M, Ide T, Wu Z, Ochi-Shindou M, Kanki T, Kang D, Sunagawa K, Tsutsui H and Nakanishi H: Reverse of age-dependent memory impairment and mitochondrial DNA damage in microglia by an overexpression of human mitochondrial transcription factor a in mice. J Neurosci. 28:8624–8634. 2008. View Article : Google Scholar : PubMed/NCBI

183 

Oka S, Leon J, Sakumi K, Ide T, Kang D, LaFerla FM and Nakabeppu Y: Human mitochondrial transcriptional factor A breaks the mitochondria-mediated vicious cycle in Alzheimer's disease. Sci Rep. 6:378892016. View Article : Google Scholar : PubMed/NCBI

184 

Ylikallio E, Tyynismaa H, Tsutsui H, Ide T and Suomalainen A: High mitochondrial DNA copy number has detrimental effects in mice. Hum Mol Genet. 19:2695–2705. 2010. View Article : Google Scholar : PubMed/NCBI

185 

Kleih M, Böpple K, Dong M, Gaißler A, Heine S, Olayioye MA, Aulitzky WE and Essmann F: Direct impact of cisplatin on mitochondria induces ROS production that dictates cell fate of ovarian cancer cells. Cell Death Dis. 10:8512019. View Article : Google Scholar : PubMed/NCBI

186 

Kubo Y, Tanaka K, Masuike Y, Takahashi T, Yamashita K, Makino T, Saito T, Yamamoto K, Tsujimoto T, Harino T, et al: Low mitochondrial DNA copy number induces chemotherapy resistance via epithelial-mesenchymal transition by DNA methylation in esophageal squamous cancer cells. J Transl Med. 20:3832022. View Article : Google Scholar : PubMed/NCBI

187 

Mei H, Sun S, Bai Y, Chen Y, Chai R and Li H: Reduced mtDNA copy number increases the sensitivity of tumor cells to chemotherapeutic drugs. Cell Death Dis. 6:e17102015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Mohamed Yusoff A, Mohd Khair S and Abd Radzak S: Mitochondrial DNA copy number alterations: Key players in the complexity of glioblastoma (Review). Mol Med Rep 31: 78, 2025.
APA
Mohamed Yusoff, A., Mohd Khair, S., & Abd Radzak, S. (2025). Mitochondrial DNA copy number alterations: Key players in the complexity of glioblastoma (Review). Molecular Medicine Reports, 31, 78. https://doi.org/10.3892/mmr.2025.13443
MLA
Mohamed Yusoff, A., Mohd Khair, S., Abd Radzak, S."Mitochondrial DNA copy number alterations: Key players in the complexity of glioblastoma (Review)". Molecular Medicine Reports 31.3 (2025): 78.
Chicago
Mohamed Yusoff, A., Mohd Khair, S., Abd Radzak, S."Mitochondrial DNA copy number alterations: Key players in the complexity of glioblastoma (Review)". Molecular Medicine Reports 31, no. 3 (2025): 78. https://doi.org/10.3892/mmr.2025.13443
Copy and paste a formatted citation
x
Spandidos Publications style
Mohamed Yusoff A, Mohd Khair S and Abd Radzak S: Mitochondrial DNA copy number alterations: Key players in the complexity of glioblastoma (Review). Mol Med Rep 31: 78, 2025.
APA
Mohamed Yusoff, A., Mohd Khair, S., & Abd Radzak, S. (2025). Mitochondrial DNA copy number alterations: Key players in the complexity of glioblastoma (Review). Molecular Medicine Reports, 31, 78. https://doi.org/10.3892/mmr.2025.13443
MLA
Mohamed Yusoff, A., Mohd Khair, S., Abd Radzak, S."Mitochondrial DNA copy number alterations: Key players in the complexity of glioblastoma (Review)". Molecular Medicine Reports 31.3 (2025): 78.
Chicago
Mohamed Yusoff, A., Mohd Khair, S., Abd Radzak, S."Mitochondrial DNA copy number alterations: Key players in the complexity of glioblastoma (Review)". Molecular Medicine Reports 31, no. 3 (2025): 78. https://doi.org/10.3892/mmr.2025.13443
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team