Mitochondrial OPA1, Apoptosis, and Heart Failure

Overview

Journal Cardiovasc Res

Specialty Cardiology & Vascular Diseases

Date 2009 Jun 5

PMID 19493956

Citations 206

Authors

Le Chen

Qizhi Gong

James P Stice

Anne A Knowlton

Affiliations

Soon will be listed here.

Abstract

Aims: Mitochondrial fusion and fission are essential processes for preservation of normal mitochondrial function. We hypothesized that fusion proteins would be decreased in heart failure (HF), as the mitochondria in HF have been reported to be small and dysfunctional.

Methods And Results: Expression of optic atrophy 1 (OPA1), a mitochondrial fusion protein, was decreased in both human and rat HF, as observed by western blotting. OPA1 is important for maintaining normal cristae structure and function, for preserving the inner membrane structure and for protecting cells from apoptosis. Confocal and electron microscopy studies demonstrated that the mitochondria in the failing hearts were small and fragmented, consistent with decreased fusion. OPA1 mRNA levels did not differ between failing and normal hearts, suggesting post-transcriptional control. Simulated ischaemia in the cardiac myogenic cell line H9c2 cells reduced OPA protein levels. Reduction of OPA1 expression with shRNA resulted in increased apoptosis and fragmentation of the mitochondria. Overexpression of OPA1 increased mitochondrial tubularity, but did not protect against simulated ischaemia-induced apoptosis. Cytochrome c release from the mitochondria was increased both with reduction in OPA1 and with overexpression of OPA1.

Conclusion: This is the first report, to our knowledge, of changes in mitochondrial fusion/fission proteins in cardiovascular disease. These changes have implications for mitochondrial function and apoptosis, contributing to the cell loss which is part of the downward progression of the failing heart.

Citing Articles

Molecular Mechanisms Underlying Heart Failure and Their Therapeutic Potential.

Fonseka O, Gare S, Chen X, Zhang J, Alatawi N, Ross C Cells. 2025; 14(5).

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Mitochondria-associated endoplasmic reticulum membranes and myocardial ischemia: from molecular mechanisms to therapeutic strategies.

Chen C, Dai G, Fan M, Wang X, Niu K, Gao W J Transl Med. 2025; 23(1):277.

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Ultrastructure analysis of mitochondria, lipid droplet and sarcoplasmic reticulum apposition in human heart failure.

Latchman N, Stevens T, Bedi K, Prosser B, Margulies K, Elrod J bioRxiv. 2025; .

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Creating Optimal Western Blot Conditions for OPA1 Isoforms in Skeletal Muscle Cells and Tissue.

Mungai M, Crabtree A, Le H, Moore J, Nguyen D, Rodriguez B Curr Protoc. 2025; 5(2):e70004.

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Cardiac effects of OPA1 protein promotion in a transgenic animal model.

Bruszt K, Horvath O, Ordog K, Toth S, Juhasz K, Vamos E PLoS One. 2024; 19(11):e0310394.

PMID: 39570915 PMC: 11581344. DOI: 10.1371/journal.pone.0310394.

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