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Organelle homeostasis disruption: A driving force in the progression of cardiomyopathy (Review)

  • Authors:
    • Yuxing Hou
    • Chao Li
    • Youyou Chen
    • Danfeng Zhong
    • Miaomiao Chai
    • Lijiao Mo
    • Senna Lin
    • Fangfang Huang
    • Qi Chen
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Deqing People's Hospital, Huzhou, Zhejiang 313216, P.R. China, Department of Anesthesiology, Shanxi Provincial People's Hospital Affiliated Shanxi Medical University, Taiyuan, Shanxi 030012, P.R. China, Department of Cardiology, Wenling Hospital of Wenzhou Medical University, Taizhou, Zhejiang 317500, P.R. China, Department of Cardiology, Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, P.R. China, Department of Cardiology, Deqing People's Hospital, Huzhou, Zhejiang 313216, P.R. China
    Copyright: © Hou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 118
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    Published online on: February 26, 2026
       https://doi.org/10.3892/etm.2026.13113
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Abstract

Cardiomyopathy is a complex heart disease with structural and functional defects of the myocardium, often leading to poor clinical outcomes. While traditional research has focused on myofibrillar pathology and ion channel dysfunction, emerging evidence indicates that organelle homeostasis serves a central role in the pathogenesis of the disease. Mitochondrial dysfunction disrupts energy metabolism, calcium handling, dynamics and mitophagy. Golgi fragmentation, impaired glycosylation and abnormal vesicular trafficking jeopardize protein maturation and secretion. Endoplasmic reticulum stress causes myocardial injury via unfolded protein response, calcium dyshomeostasis and disruptions of lipid metabolism. Lysosomal degradation is disrupted by autophagic dysfunction, enzyme dysregulation and calcium signaling abnormalities. Ribosomes regulate proteostasis by defective biogenesis, quality control and translational dysregulation. Nuclear envelope instability and intercalated disc dysfunction disrupt normal mechanical and gene regulation in the development of cardiomyopathy. In combination, these findings support the concept of cardiomyopathy as a multi‑organelle network disease driven by coordinated dysfunction of interconnected organelles. This review systematically summarizes current evidence on organelle‑specific and inter‑organelle mechanisms underlying cardiomyopathy, highlighting how disrupted organelle homeostasis collectively contributes to disease initiation and progression.
View Figures

Figure 1

Schematic illustration of
mitochondrial dysfunction in the pathogenesis of cardiomyopathy.
Defective mitochondrial metabolism and dynamics induce oxidative
stress, calcium imbalance, apoptosis and inflammation, ultimately
contributing to cardiac remodeling and functional decline. ATP,
adenosine triphosphate; MOF, males absent on the first; CPT2,
carnitine palmitoyltransferase 2; ROS, reactive oxygen species;
mtDNA, mitochondrial DNA; MCU, mitochondrial calcium uniporter;
CaMKII, calcium/calmodulin-dependent protein kinase II; cAMP,
cyclic adenosine monophosphate; PTP, permeability transition pore;
MFN2, mitofusin 2; OPA1, mitochondrial dynamin-like GTPase; Drp1,
dynamin-related protein 1; PINK1, PTEN-induced kinase 1.

Figure 2

Schematic illustration showing the
role of the Golgi apparatus in cardiomyopathy pathogenesis. Golgi
apparatus dysfunction disrupts protein trafficking, glycosylation,
vesicular transport and autophagy, resulting in endoplasmic
reticulum stress, impaired sarcomere organization and altered
secretion of extracellular matrix proteins. These alterations
contribute to cardiomyocyte hypertrophy, apoptosis and maladaptive
cardiac remodeling, ultimately promoting the progression of
cardiomyopathy. ROS, reactive oxygen species; MGAT1,
α-1,3-mannosyl-glycoprotein 2-β-N-acetylglucosaminyltransferase;
GALNT1, polypeptide N-acetylgalactosaminyltransferase 1; OGA,
O-GlcNAcase; ATG, autophagy-related protein; YIPF3/4, Yip1 domain
family member 3/4; AP1/4, adaptor protein complex 1/4.
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Copy and paste a formatted citation
Spandidos Publications style
Hou Y, Li C, Chen Y, Zhong D, Chai M, Mo L, Lin S, Huang F and Chen Q: Organelle homeostasis disruption: A driving force in the progression of cardiomyopathy (Review). Exp Ther Med 31: 118, 2026.
APA
Hou, Y., Li, C., Chen, Y., Zhong, D., Chai, M., Mo, L. ... Chen, Q. (2026). Organelle homeostasis disruption: A driving force in the progression of cardiomyopathy (Review). Experimental and Therapeutic Medicine, 31, 118. https://doi.org/10.3892/etm.2026.13113
MLA
Hou, Y., Li, C., Chen, Y., Zhong, D., Chai, M., Mo, L., Lin, S., Huang, F., Chen, Q."Organelle homeostasis disruption: A driving force in the progression of cardiomyopathy (Review)". Experimental and Therapeutic Medicine 31.5 (2026): 118.
Chicago
Hou, Y., Li, C., Chen, Y., Zhong, D., Chai, M., Mo, L., Lin, S., Huang, F., Chen, Q."Organelle homeostasis disruption: A driving force in the progression of cardiomyopathy (Review)". Experimental and Therapeutic Medicine 31, no. 5 (2026): 118. https://doi.org/10.3892/etm.2026.13113
Copy and paste a formatted citation
x
Spandidos Publications style
Hou Y, Li C, Chen Y, Zhong D, Chai M, Mo L, Lin S, Huang F and Chen Q: Organelle homeostasis disruption: A driving force in the progression of cardiomyopathy (Review). Exp Ther Med 31: 118, 2026.
APA
Hou, Y., Li, C., Chen, Y., Zhong, D., Chai, M., Mo, L. ... Chen, Q. (2026). Organelle homeostasis disruption: A driving force in the progression of cardiomyopathy (Review). Experimental and Therapeutic Medicine, 31, 118. https://doi.org/10.3892/etm.2026.13113
MLA
Hou, Y., Li, C., Chen, Y., Zhong, D., Chai, M., Mo, L., Lin, S., Huang, F., Chen, Q."Organelle homeostasis disruption: A driving force in the progression of cardiomyopathy (Review)". Experimental and Therapeutic Medicine 31.5 (2026): 118.
Chicago
Hou, Y., Li, C., Chen, Y., Zhong, D., Chai, M., Mo, L., Lin, S., Huang, F., Chen, Q."Organelle homeostasis disruption: A driving force in the progression of cardiomyopathy (Review)". Experimental and Therapeutic Medicine 31, no. 5 (2026): 118. https://doi.org/10.3892/etm.2026.13113
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