Understanding the impact of mitochondrial DNA mutations on aging and carcinogenesis (Review)
- Authors:
- Hiroshi Kobayashi
- Shogo Imanaka
-
Affiliations: Department of Gynecology and Reproductive Medicine, Ms.Clinic MayOne, Kashihara, Nara 634‑0813, Japan - Published online on: June 3, 2025 https://doi.org/10.3892/ijmm.2025.5559
- Article Number: 118
-
Copyright: © Kobayashi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
 |
 |
 |
|
Sun N, Youle RJ and Finkel T: The mitochondrial basis of aging. Mol Cell. 61:654–666. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Wallace DC: A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: A dawn for evolutionary medicine. Annu Rev Genet. 39:359–407. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Elliott HR, Samuels DC, Eden JA, Relton CL and Chinnery PF: Pathogenic mitochondrial DNA mutations are common in the general population. Am J Hum Genet. 83:254–260. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Lee HC, Chang CM and Chi CW: Somatic mutations of mitochondrial DNA in aging and cancer progression. Ageing Res Rev. 9(Suppl 1): S47–S58. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Stewart JB and Chinnery PF: Extreme heterogeneity of human mitochondrial DNA from organelles to populations. Nat Rev Genet. 22:106–118. 2021. View Article : Google Scholar | |
|
Cote-L'Heureux A, Maithania YNK, Franco M and Khrapko K: Are some mutations more equal than others? Elife. 12:e871942023. View Article : Google Scholar : PubMed/NCBI | |
|
Kowaltowski AJ: Alternative mitochondrial functions in cell physiopathology: Beyond ATP production. Braz J Med Biol Res. 33:241–250. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Sanchez-Contreras M, Sweetwyne MT, Tsantilas KA, Whitson JA, Campbell MD, Kohrn BF, Kim HJ, Hipp MJ, Fredrickson J, Nguyen MM, et al: The multi-tissue landscape of somatic mtDNA mutations indicates tissue-specific accumulation and removal in aging. Elife. 12:e833952023. View Article : Google Scholar : PubMed/NCBI | |
|
Lawless C, Greaves L, Reeve AK, Turnbull DM and Vincent AE: The rise and rise of mitochondrial DNA mutations. Open Biol. 10:2000612020. View Article : Google Scholar : PubMed/NCBI | |
|
Pérez-Amado CJ, Bazan-Cordoba A, Hidalgo-Miranda A and Jiménez-Morales S: Mitochondrial heteroplasmy shifting as a potential biomarker of cancer progression. Int J Mol Sci. 22:73692021. View Article : Google Scholar : PubMed/NCBI | |
|
Khrapko K, Coller H, André P, Li XC, Foret F, Belenky A, Karger BL and Thilly WG: Mutational spectrometry without phenotypic selection: human mitochondrial DNA. Nucleic Acids Res. 25:685–693. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Shokolenko I and Alexeyev M: Mitochondrial DNA: Consensuses and controversies. DNA (Basel). 2:131–148. 2022.PubMed/NCBI | |
|
Wallace DC: Mitochondrial diseases in man and mouse. Science. 283:1482–1488. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Youle RJ and Narendra DP: Mechanisms of mitophagy. Nat Rev Mol Cell Biol. 12:9–14. 2011. View Article : Google Scholar | |
|
Rossignol R, Faustin B, Rocher C, Malgat M, Mazat JP and Letellier T: Mitochondrial threshold effects. Biochem J. 370:751–762. 2003. View Article : Google Scholar | |
|
De Giorgi C and Saccone C: Mitochondrial genome in animal cells. Structure, organization, and evolution. Cell Biophys. 14:67–78. 1989. View Article : Google Scholar : PubMed/NCBI | |
|
Gorelick AN, Kim M, Chatila WK, La K, Hakimi AA, Berger MF, Taylor BS, Gammage PA and Reznik E: Respiratory complex and tissue lineage drive recurrent mutations in tumour mtDNA. Nat Metab. 3:558–570. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Young MJ and Copeland WC: Human mitochondrial DNA replication machinery and disease. Curr Opin Genet Dev. 38:52–62. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Kobayashi H, Matsubara S, Yoshimoto C, Shigetomi H and Imanaka S: A comprehensive review of the contribution of mitochondrial DNA mutations and dysfunction in polycystic ovary syndrome, supported by secondary database analysis. Int J Mol Sci. 26:11722025. View Article : Google Scholar : PubMed/NCBI | |
|
Zaidi AA, Wilton PR, Su MSW, Paul IM, Arbeithuber B, Anthony K, Nekrutenko A, Nielsen R and Makova KD: Bottleneck and selection in the germline and maternal age influence transmission of mitochondrial DNA in human pedigrees. Proc Natl Acad Sci USA. 116:25172–25178. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Kopinski PK, Singh LN, Zhang S, Lott MT and Wallace DC: Mitochondrial DNA variation and cancer. Nat Rev Cancer. 21:431–445. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Khadka P, Young CKJ, Sachidanandam R, Brard L and Young MJ: Our current understanding of the biological impact of endometrial cancer mtDNA genome mutations and their potential use as a biomarker. Front Oncol. 14:13946992024. View Article : Google Scholar : PubMed/NCBI | |
|
Guo X, Xu W, Zhang W, Pan C, Thalacker-Mercer AE, Zheng H and Gu Z: High-frequency and functional mitochondrial DNA mutations at the single-cell level. Proc Natl Acad Sci USA. 120:e22015181202023. View Article : Google Scholar : | |
|
Schaack S, Ho EKH and Macrae F: Disentangling the intertwined roles of mutation, selection and drift in the mitochondrial genome. Philos Trans R Soc Lond B Biol Sci. 375:201901732020. View Article : Google Scholar : | |
|
Medeiros DM: Assessing mitochondria biogenesis. Methods. 46:288–294. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
McKinney EA and Oliveira MT: Replicating animal mitochondrial DNA. Genet Mol Biol. 36:308–315. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Jornayvaz FR and Shulman GI: Regulation of mitochondrial biogenesis. Essays Biochem. 47:69–84. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Scarpulla RC: Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev. 88:611–638. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Yin PH, Lee HC, Chau GY, Wu YT, Li SH, Lui WY, Wei YH, Liu TY and Chi CW: Alteration of the copy number and deletion of mitochondrial DNA in human hepatocellular carcinoma. Br J Cancer. 90:2390–2396. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Lee HC, Huang KH, Yeh TS and Chi CW: Somatic alterations in mitochondrial DNA and mitochondrial dysfunction in gastric cancer progression. World J Gastroenterol. 20:3950–3959. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
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 | |
|
El-Hattab AW, Craigen WJ and Scaglia F: Mitochondrial DNA maintenance defects. Biochim Biophys Acta Mol Basis Dis. 1863:1539–1555. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Alberghina L: The Warburg effect explained: integration of enhanced glycolysis with heterogeneous mitochondria to promote cancer cell proliferation. Int J Mol Sci. 24:157872023. View Article : Google Scholar : PubMed/NCBI | |
|
Soga T: Cancer metabolism: Key players in metabolic reprogramming. Cancer Sci. 104:275–281. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Brandon M, Baldi P and Wallace DC: Mitochondrial mutations in cancer. Oncogene. 25:4647–4662. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Li T, Copeland C and Le A: Glutamine metabolism in cancer. Adv Exp Med Biol. 1311:17–38. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Selak MA, Armour SM, MacKenzie ED, Boulahbel H, Watson DG, Mansfield KD, Pan Y, Simon MC, Thompson CB and Gottlieb E: Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell. 7:77–85. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Lu J, Sharma LK and Bai Y: Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis. Cell Res. 19:802–815. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Reinsalu L, Puurand M, Chekulayev V, Miller S, Shevchuk I, Tepp K, Rebane-Klemm E, Timohhina N, Terasmaa A and Kaambre T: Energy metabolic plasticity of colorectal cancer cells as a determinant of tumor growth and metastasis. Front Oncol. 11:6989512021. View Article : Google Scholar : PubMed/NCBI | |
|
Yapa NMB, Lisnyak V, Reljic B and Ryan MT: Mitochondrial dynamics in health and disease. FEBS Lett. 595:1184–1204. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Mao H, Chen W, Chen L and Li L: Potential role of mitochondria-associated endoplasmic reticulum membrane proteins in diseases. Biochem Pharmacol. 199:1150112022. View Article : Google Scholar : PubMed/NCBI | |
|
St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jäger S, Handschin C, Zheng K, Lin J, Yang W, et al: Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell. 127:397–408. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Butow RA and Avadhani NG: Mitochondrial signaling: The retrograde response. Mol Cell. 14:1–15. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Ke R, Xu Q, Li C, Luo L and Huang D: Mechanisms of AMPK in the maintenance of ATP balance during energy metabolism. Cell Biol Int. 42:384–392. 2018. View Article : Google Scholar | |
|
Morgan MJ and Liu ZG: Crosstalk of reactive oxygen species and NF-κB signaling. Cell Res. 21:103–115. 2011. View Article : Google Scholar | |
|
Murphy MP: How mitochondria produce reactive oxygen species. Biochem J. 417:1–13. 2009. View Article : Google Scholar | |
|
Rampazzo C, Ferraro P, Pontarin G, Fabris S, Reichard P and Bianchi V: Mitochondrial deoxyribonucleotides, pool sizes, synthesis, and regulation. J Biol Chem. 279:17019–17026. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Xiao M, Yang H, Xu W, Ma S, Lin H, Zhu H, Liu L, Liu Y, Yang C, Xu Y, et al: Inhibition of α-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev. 26:1326–1338. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Macián F, López-Rodríguez C and Rao A: Partners in transcription: NFAT and AP-1. Oncogene. 20:2476–2489. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Vijg J, Schumacher B, Abakir A, Antonov M, Bradley C, Cagan A, Church G, Gladyshev VN, Gorbunova V, Maslov AY, et al: Mitigating age-related somatic mutation burden. Trends Mol Med. 29:530–540. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Arbeithuber B, Hester J, Cremona MA, Stoler N, Zaidi A, Higgins B, Anthony K, Chiaromonte F, Diaz FJ and Makova KD: Age-related accumulation of de novo mitochondrial mutations in mammalian oocytes and somatic tissues. PLoS Biol. 18:e30007452020. View Article : Google Scholar : PubMed/NCBI | |
|
Abascal F, Harvey LMR, Mitchell E, Lawson ARJ, Lensing SV, Ellis P, Russell AJC, Alcantara RE, Baez-Ortega A, Wang Y, et al: Somatic mutation landscapes at single-molecule resolution. Nature. 593:405–410. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Arbeithuber B, Cremona MA, Hester J, Barrett A, Higgins B, Anthony K, Chiaromonte F, Diaz FJ and Makova KD: Advanced age increases frequencies of de novo mitochondrial mutations in macaque oocytes and somatic tissues. Proc Natl Acad Sci USA. 119:e21187401192022. View Article : Google Scholar : PubMed/NCBI | |
|
Ahn EH, Hirohata K, Kohrn BF, Fox EJ, Chang CC and Loeb LA: Detection of ultra-rare mitochondrial mutations in breast stem cells by duplex sequencing. PLoS One. 10:e01362162015. View Article : Google Scholar : PubMed/NCBI | |
|
Salk JJ, Schmitt MW and Loeb LA: Enhancing the accuracy of next-generation sequencing for detecting rare and subclonal mutations. Nat Rev Genet. 19:269–285. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Kennedy SR, Salk JJ, Schmitt MW and Loeb LA: Ultra-sensitive sequencing reveals an age-related increase in somatic mitochondrial mutations that are inconsistent with oxidative damage. PLoS Genet. 9:e10037942013. View Article : Google Scholar : PubMed/NCBI | |
|
Sanchez-Contreras M, Sweetwyne MT, Kohrn BF, Tsantilas KA, Hipp MJ, Schmidt EK, Fredrickson J, Whitson JA, Campbell MD, Rabinovitch PS, et al: A replication-linked mutational gradient drives somatic mutation accumulation and influences germline polymorphisms and genome composition in mitochondrial DNA. Nucleic Acids Res. 49:11103–11118. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Foury F, Hu J and Vanderstraeten S: Mitochondrial DNA mutators. Cell Mol Life Sci. 61:2799–2811. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
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 | |
|
Tanaka M and Ozawa T: Strand asymmetry in human mitochondrial DNA mutations. Genomics. 22:327–335. 1994. View Article : Google Scholar : PubMed/NCBI | |
|
Garesse R: Drosophila melanogaster mitochondrial DNA: Gene organization and evolutionary considerations. Genetics. 118:649–663. 1988. View Article : Google Scholar : PubMed/NCBI | |
|
Spelbrink JN, Toivonen JM, Hakkaart GA, Kurkela JM, Cooper HM, Lehtinen SK, Lecrenier N, Back JW, Speijer D, Foury F and Jacobs HT: In vivo functional analysis of the human mitochondrial DNA polymerase POLG expressed in cultured human cells. J Biol Chem. 275:24818–24828. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Ju YS, Alexandrov LB, Gerstung M, Martincorena I, Nik-Zainal S, Ramakrishna M, Davies HR, Papaemmanuil E, Gundem G, Shlien A, et al: Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer. Elife. 3:e029352014. View Article : Google Scholar : PubMed/NCBI | |
|
McMahon S and LaFramboise T: Mutational patterns in the breast cancer mitochondrial genome, with clinical correlates. Carcinogenesis. 35:1046–1054. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Baker KT, Nachmanson D, Kumar S, Emond MJ, Ussakli C, Brentnall TA, Kennedy SR and Risques RA: Mitochondrial DNA mutations are associated with ulcerative colitis preneoplasia but tend to be negatively selected in cancer. Mol Cancer Res. 17:488–498. 2019. View Article : Google Scholar : | |
|
Chen XZ, Fang Y, Shi YH, Cui JH, Li LY, Xu YC and Ling B: Deciphering the spectrum of somatic mutations in the entire mitochondrial DNA genome. Genet Mol Res. 14:4331–4337. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Otten ABC and Smeets HJM: Evolutionary defined role of the mitochondrial DNA in fertility, disease and ageing. Hum Reprod Update. 21:671–689. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Suen DF, Narendra DP, Tanaka A, Manfredi G and Youle RJ: Parkin overexpression selects against a deleterious mtDNA mutation in heteroplasmic cybrid cells. Proc Natl Acad Sci USA. 107:11835–11840. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Ferreira T and Rodriguez S: Mitochondrial DNA: Inherent complexities relevant to genetic analyses. Genes (Basel). 15:6172024. View Article : Google Scholar : PubMed/NCBI | |
|
Hong YS, Battle SL, Shi W, Puiu D, Pillalamarri V, Xie J, Pankratz N, Lake NJ, Lek M, Rotter JI, et al: Deleterious heteroplasmic mitochondrial mutations are associated with an increased risk of overall and cancer-specific mortality. Nat Commun. 14:61132023. View Article : Google Scholar : PubMed/NCBI | |
|
Ye K, Lu J, Ma F, Keinan A and Gu Z: Extensive pathogenicity of mitochondrial heteroplasmy in healthy human individuals. Proc Natl Acad Sci USA. 111:10654–10659. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
López-Otín C, Blasco MA, Partridge L, Serrano M and Kroemer G: The hallmarks of aging. Cell. 153:1194–1217. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Walker MA, Lareau CA, Ludwig LS, Karaa A, Sankaran VG, Regev A and Mootha VK: Purifying selection against pathogenic mitochondrial DNA in human T cells. N Engl J Med. 383:1556–1563. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Arbeithuber B, Anthony K, Higgins B, Oppelt P, Shebl O, Tiemann-Boege I, Chiaromonte F, Ebner T and Makova KD: Mitochondrial DNA mutations in human oocytes undergo frequency-dependent selection but do not increase with age. bioRxiv [Preprint]: 2024.12.09.627454. 2024. | |
|
Monnat RJ Jr, Maxwell CL and Loeb LA: Nucleotide sequence preservation of human leukemic mitochondrial DNA. Cancer Res. 45:1809–1814. 1985.PubMed/NCBI | |
|
Wang CY, Wang HW, Yao YG, Kong QP and Zhang YP: Somatic mutations of mitochondrial genome in early stage breast cancer. Int J Cancer. 121:1253–1256. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Chatterjee A, Dasgupta S and Sidransky D: Mitochondrial subversion in cancer. Cancer Prev Res (Phila). 4:638–654. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Bandelt HJ, Salas A and Bravi CM: What is a 'novel' mtDNA mutation-and does 'novelty' really matter? J Hum Genet. 51:1073–1082. 2006. View Article : Google Scholar | |
|
Hung WY, Wu CW, Yin PH, Chang CJ, Li AF, Chi CW, Wei YH and Lee HC: Somatic mutations in mitochondrial genome and their potential roles in the progression of human gastric cancer. Biochim Biophys Acta. 1800:264–270. 2010. View Article : Google Scholar | |
|
Kassauei K, Habbe N, Mullendore ME, Karikari CA, Maitra A and Feldmann G: Mitochondrial DNA mutations in pancreatic cancer. Int J Gastrointest Cancer. 37:57–64. 2006. View Article : Google Scholar | |
|
Hashizume O, Shimizu A, Yokota M, Sugiyama A, Nakada K, Miyoshi H, Itami M, Ohira M, Nagase H, Takenaga K and Hayashi JI: Specific mitochondrial DNA mutation in mice regulates diabetes and lymphoma development. Proc Natl Acad Sci USA. 109:10528–10533. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Yin C, Li DY, Guo X, Cao HY, Chen YB, Zhou F, Ge NJ, Liu Y, Guo SS, Zhao Z, et al: NGS-based profiling reveals a critical contributing role of somatic D-loop mtDNA mutations in HBV-related hepatocarcinogenesis. Ann Oncol. 30:953–962. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Kwon S, Kim SS, Nebeck HE and Ahn EH: Immortalization of different breast epithelial cell types results in distinct mitochondrial mutagenesis. Int J Mol Sci. 20:28132019. View Article : Google Scholar : PubMed/NCBI | |
|
Kamalidehghan B, Houshmand M, Ismail P, Panahi MSS and Akbari MHH: Delta mtDNA4977 is more common in non-tumoral cells from gastric cancer sample. Arch Med Res. 37:730–735. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Dai JG, Xiao YB, Min JX, Zhang GQ, Yao K and Zhou RJ: Mitochondrial DNA 4977 BP deletion mutations in lung carcinoma. Indian J Cancer. 43:20–25. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
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 | |
|
Li Y, Sundquist K, Vats S, Hong MG, Wang X, Chen Y, Hedelius A, Saal LH, Sundquist J and Memon AA: Mitochondrial heteroplasmic shifts reveal a positive selection of breast cancer. J Transl Med. 21:6962023. View Article : Google Scholar : PubMed/NCBI | |
|
Bjørnetrø T, Bousquet PA, Redalen KR, Trøseid AMS, Lüders T, Stang E, Sanabria AM, Johansen C, Fuglestad AJ, Kersten C, et al: Next-generation sequencing reveals mitogenome diversity in plasma extracellular vesicles from colorectal cancer patients. BMC Cancer. 23:6502023. View Article : Google Scholar : PubMed/NCBI | |
|
Zheng W, Khrapko K, Coller HA, Thilly WG and Copeland WC: Origins of human mitochondrial point mutations as DNA polymerase gamma-mediated errors. Mutat Res. 599:11–20. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Itsara LS, Kennedy SR, Fox EJ, Yu S, Hewitt JJ, Sanchez-Contreras M, Cardozo-Pelaez F and Pallanck LJ: Oxidative stress is not a major contributor to somatic mitochondrial DNA mutations. PLoS Genet. 10:e10039742014. View Article : Google Scholar : PubMed/NCBI | |
|
Hoekstra JG, Hipp MJ, Montine TJ and Kennedy SR: Mitochondrial DNA mutations increase in early stage Alzheimer disease and are inconsistent with oxidative damage. Ann Neurol. 80:301–306. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Ameur A, Stewart JB, Freyer C, Hagström E, Ingman M, Larsson NG and Gyllensten U: Ultra-deep sequencing of mouse mitochondrial DNA: Mutational patterns and their origins. PLoS Genet. 7:e10020282011. View Article : Google Scholar : PubMed/NCBI | |
|
Samstag CL, Hoekstra JG, Huang CH, Chaisson MJ, Youle RJ, Kennedy SR and Pallanck LJ: Deleterious mitochondrial DNA point mutations are overrepresented in Drosophila expressing a proofreading-defective DNA polymerase γ. PLoS Genet. 14:e10078052018. View Article : Google Scholar | |
|
Andreazza S, Samstag CL, Sanchez-Martinez A, Fernandez-Vizarra E, Gomez-Duran A, Lee JJ, Tufi R, Hipp MJ, Schmidt EK, Nicholls TJ, et al: Mitochondrially-targeted APOBEC1 is a potent mtDNA mutator affecting mitochondrial function and organismal fitness in Drosophila. Nat Commun. 10:32802019. View Article : Google Scholar : PubMed/NCBI | |
|
Shukla P, Mukherjee S and Patil A: Identification of variants in mitochondrial D-loop and OriL region and analysis of mitochondrial DNA copy number in women with polycystic ovary syndrome. DNA Cell Biol. 39:1458–1466. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Toure S, Mbaye F, Gueye MD, Fall M, Dem A, Lamy JB and Sembene M: Somatic mitochondrial mutations in oral cavity cancers among senegalese patients. Asian Pac J Cancer Prev. 20:2203–2208. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Waneka G, Svendsen JM, Havird JC and Sloan DB: Mitochondrial mutations in Caenorhabditis elegans show signatures of oxidative damage and an AT-bias. Genetics. 219:iyab1162021. View Article : Google Scholar : PubMed/NCBI | |
|
Taylor RW, Barron MJ, Borthwick GM, Gospel A, Chinnery PF, Samuels DC, Taylor GA, Plusa SM, Needham SJ, Greaves LC, et al: Mitochondrial DNA mutations in human colonic crypt stem cells. J Clin Invest. 112:1351–1360. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Blackwood JK, Williamson SC, Greaves LC, Wilson L, Rigas AC, Sandher R, Pickard RS, Robson CN, Turnbull DM, Taylor RW and Heer R: In situ lineage tracking of human prostatic epithelial stem cell fate reveals a common clonal origin for basal and luminal cells. J Pathol. 225:181–188. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Abu-Amero KK, Alzahrani AS, Zou M and Shi Y: High frequency of somatic mitochondrial DNA mutations in human thyroid carcinomas and complex I respiratory defect in thyroid cancer cell lines. Oncogene. 24:1455–1460. 2005. View Article : Google Scholar | |
|
Abu-Amero KK, Alzahrani AS, Zou M and Shi Y: Association of mitochondrial DNA transversion mutations with familial medullary thyroid carcinoma/multiple endocrine neoplasia type 2 syndrome. Oncogene. 25:677–684. 2006. View Article : Google Scholar | |
|
Wang B, Qiao L, Wang Y, Zeng J, Chen D, Guo H and Zhang Y: Mitochondrial DNA D-loop lesions with the enhancement of DNA repair contribute to gastrointestinal cancer progression. Oncol Rep. 40:3694–3704. 2018.PubMed/NCBI | |
|
Zeng AGX, Leung ACY and Brooks-Wilson AR: Somatic mitochondrial DNA mutations in diffuse large B-cell lymphoma. Sci Rep. 8:36232018. View Article : Google Scholar : PubMed/NCBI | |
|
Vikramdeo KS, Anand S, Sudan SK, Pramanik P, Singh S, Godwin AK, Singh AP and Dasgupta S: Profiling mitochondrial DNA mutations in tumors and circulating extracellular vesicles of triple-negative breast cancer patients for potential biomarker development. FASEB Bioadv. 5:412–426. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Dani MAC, Dani SU, Lima SPG, Martinez A, Rossi BM, Soares F, Zago MA and Simpson AJ: Less DeltamtDNA4977 than normal in various types of tumors suggests that cancer cells are essentially free of this mutation. Genet Mol Res. 3:395–409. 2004.PubMed/NCBI | |
|
Young MJ, Sachidanandam R, Hales DB, Brard L, Robinson K, Rahman MM, Khadka P, Groesch K and Young CKJ: Identification of somatic mitochondrial DNA mutations, heteroplasmy, and increased levels of catenanes in tumor specimens obtained from three endometrial cancer patients. Life (Basel). 12:5622022.PubMed/NCBI | |
|
Martínez-Reyes I, Cardona LR, Kong H, Vasan K, McElroy GS, Werner M, Kihshen H, Reczek CR, Weinberg SE, Gao P, et al: Mitochondrial ubiquinol oxidation is necessary for tumour growth. Nature. 585:288–292. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Ericson NG, Kulawiec M, Vermulst M, Sheahan K, O'Sullivan J, Salk JJ and Bielas JH: Decreased mitochondrial DNA mutagenesis in human colorectal cancer. PLoS Genet. 8:e10026892012. View Article : Google Scholar : PubMed/NCBI | |
|
Mithani SK, Taube JM, Zhou S, Smith IM, Koch WM, Westra WH and Califano JA: Mitochondrial mutations are a late event in the progression of head and neck squamous cell cancer. Clin Cancer Res. 13:4331–4335. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Ahn EH, Lee SH, Kim JY, Chang CC and Loeb LA: Decreased mitochondrial mutagenesis during transformation of human breast stem cells into tumorigenic cells. Cancer Res. 76:4569–4578. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Li D, Du X, Guo X, Zhan L, Li X, Yin C, Chen C, Li M, Li B, Yang H and Xing J: Site-specific selection reveals selective constraints and functionality of tumor somatic mtDNA mutations. J Exp Clin Cancer Res. 36:1682017. View Article : Google Scholar : PubMed/NCBI | |
|
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 | |
|
Chang SC, Lin PC, Yang SH, Wang HS, Liang WY and Lin JK: Mitochondrial D-loop mutation is a common event in colorectal cancers with p53 mutations. Int J Colorectal Dis. 24:623–628. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
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 : | |
|
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 | |
|
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 | |
|
Maslov AY and Vijg J: Genome instability, cancer and aging. Biochim Biophys Acta. 1790:963–969. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Hall MWJ, Jones PH and Hall BA: Relating evolutionary selection and mutant clonal dynamics in normal epithelia. J R Soc Interface. 16:201902302019. View Article : Google Scholar : PubMed/NCBI | |
|
Buscarlet M, Provost S, Zada YF, Barhdadi A, Bourgoin V, Lépine G, Mollica L, Szuber N, Dubé MP and Busque L: DNMT3A and TET2 dominate clonal hematopoiesis and demonstrate benign phenotypes and different genetic predispositions. Blood. 130:753–762. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Fujino T, Goyama S, Sugiura Y, Inoue D, Asada S, Yamasaki S, Matsumoto A, Yamaguchi K, Isobe Y, Tsuchiya A, et al: Mutant ASXL1 induces age-related expansion of phenotypic hematopoietic stem cells through activation of Akt/mTOR pathway. Nat Commun. 12:18262021. View Article : Google Scholar : PubMed/NCBI | |
|
Abelson S, Collord G, Ng SWK, Weissbrod O, Mendelson Cohen N, Niemeyer E, Barda N, Zuzarte PC, Heisler L, Sundaravadanam Y, et al: Prediction of acute myeloid leukaemia risk in healthy individuals. Nature. 559:400–404. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Abby E, Dentro SC, Hall MWJ, Fowler JC, Ong SH, Sood R, Herms A, Piedrafita G, Abnizova I, Siebel CW, et al: Notch1 mutations drive clonal expansion in normal esophageal epithelium but impair tumor growth. Nat Genet. 55:232–245. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Fowler JC, King C, Bryant C, Hall MWJ, Sood R, Ong SH, Earp E, Fernandez-Antoran D, Koeppel J, Dentro SC, et al: Selection of oncogenic mutant clones in normal human skin varies with body site. Cancer Discov. 11:340–361. 2021. View Article : Google Scholar : | |
|
Testa U, Castelli G and Pelosi E: The molecular characterization of genetic abnormalities in esophageal squamous cell carcinoma may foster the development of targeted therapies. Curr Oncol. 30:610–640. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Colom B, Alcolea MP, Piedrafita G, Hall MWJ, Wabik A, Dentro SC, Fowler JC, Herms A, King C, Ong SH, et al: Spatial competition shapes the dynamic mutational landscape of normal esophageal epithelium. Nat Genet. 52:604–614. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
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 | |
|
Banik M and Adhya S: OXPHOS deficiency induces mitochondrial DNA synthesis through non-canonical AMPK-dependent mRNA compartmentalization. J Biosci. 47:672022. View Article : Google Scholar : PubMed/NCBI | |
|
Vernier M and Giguère V: Aging, senescence and mitochondria: The PGC-1/ERR axis. J Mol Endocrinol. 66:R1–R14. 2021. View Article : Google Scholar | |
|
LeBleu VS, O'Connell JT, Gonzalez Herrera KN, Wikman H, Pantel K, Haigis MC, de Carvalho FM, Damascena A, Domingos Chinen LT, Rocha RM, et al: PGC-1α mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis. Nat Cell Biol. 16(992-1003): 1–15. 2014. | |
|
Wang Y, Peng J, Yang D, Xing Z, Jiang B, Ding X, Jiang C, Ouyang B and Su L: From metabolism to malignancy: The multifaceted role of PGC1α in cancer. Front Oncol. 14:13838092024. View Article : Google Scholar | |
|
Reznick RM, Zong H, Li J, Morino K, Moore IK, Yu HJ, Liu ZX, Dong J, Mustard KJ, Hawley SA, et al: Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis. Cell Metab. 5:151–156. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang S, Wang Y, Luo L, Shi F, Zou J, Lin H, Ying Y, Luo Y, Zhan Z, Liu P, et al: AMP-activated protein kinase regulates cancer cell growth and metabolism via nuclear and mitochondria events. J Cell Mol Med. 23:3951–3961. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Chaube B, Malvi P, Singh SV, Mohammad N, Viollet B and Bhat MK: AMPK maintains energy homeostasis and survival in cancer cells via regulating p38/PGC-1α-mediated mitochondrial biogenesis. Cell Death Discov. 1:150632015. View Article : Google Scholar | |
|
Milholland B, Auton A, Suh Y and Vijg J: Age-related somatic mutations in the cancer genome. Oncotarget. 6:24627–24635. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Coller HA, Khrapko K, Bodyak ND, Nekhaeva E, Herrero-Jimenez P and Thilly WG: High frequency of homoplasmic mitochondrial DNA mutations in human tumors can be explained without selection. Nat Genet. 28:147–150. 2001. View Article : Google Scholar : PubMed/NCBI |
