Mitochondrial OPA1, apoptosis, and heart failure

Le Chen, Qizhi Gong, James P. Stice, Anne A Knowlton

Research output: Contribution to journalArticle

192 Citations (Scopus)

Abstract

AimsMitochondrial 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 resultsExpression 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.ConclusionThis 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.

Original languageEnglish (US)
Pages (from-to)91-99
Number of pages9
JournalCardiovascular Research
Volume84
Issue number1
DOIs
StatePublished - Oct 2009

Fingerprint

Autosomal Dominant Optic Atrophy
Heart Failure
Apoptosis
Mitochondria
Mitochondrial Dynamics
Ischemia
Cell Membrane Structures
Proteins
Mitochondrial Proteins
Cytochromes c
Confocal Microscopy
Small Interfering RNA
Electron Microscopy
Cardiovascular Diseases
Western Blotting
Cell Line
Messenger RNA

Keywords

  • Apoptosis
  • Fission
  • Fusion
  • Heart failure
  • Ischaemia
  • Mitochondria

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Cite this

Mitochondrial OPA1, apoptosis, and heart failure. / Chen, Le; Gong, Qizhi; Stice, James P.; Knowlton, Anne A.

In: Cardiovascular Research, Vol. 84, No. 1, 10.2009, p. 91-99.

Research output: Contribution to journalArticle

Chen, Le ; Gong, Qizhi ; Stice, James P. ; Knowlton, Anne A. / Mitochondrial OPA1, apoptosis, and heart failure. In: Cardiovascular Research. 2009 ; Vol. 84, No. 1. pp. 91-99.
@article{b70501d0c49842aa95a22dc7bfccb422,
title = "Mitochondrial OPA1, apoptosis, and heart failure",
abstract = "AimsMitochondrial 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 resultsExpression 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.ConclusionThis 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.",
keywords = "Apoptosis, Fission, Fusion, Heart failure, Ischaemia, Mitochondria",
author = "Le Chen and Qizhi Gong and Stice, {James P.} and Knowlton, {Anne A}",
year = "2009",
month = "10",
doi = "10.1093/cvr/cvp181",
language = "English (US)",
volume = "84",
pages = "91--99",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Mitochondrial OPA1, apoptosis, and heart failure

AU - Chen, Le

AU - Gong, Qizhi

AU - Stice, James P.

AU - Knowlton, Anne A

PY - 2009/10

Y1 - 2009/10

N2 - AimsMitochondrial 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 resultsExpression 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.ConclusionThis 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.

AB - AimsMitochondrial 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 resultsExpression 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.ConclusionThis 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.

KW - Apoptosis

KW - Fission

KW - Fusion

KW - Heart failure

KW - Ischaemia

KW - Mitochondria

UR - http://www.scopus.com/inward/record.url?scp=70449724857&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70449724857&partnerID=8YFLogxK

U2 - 10.1093/cvr/cvp181

DO - 10.1093/cvr/cvp181

M3 - Article

C2 - 19493956

AN - SCOPUS:70449724857

VL - 84

SP - 91

EP - 99

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 1

ER -