OPA1 mutation and late-onset cardiomyopathy: mitochondrial dysfunction and mtDNA instability.

L. Chen, Tingting Liu, Alice Tran, Xiyuan Lu, Alexey A. Tomilov, Vanessa Davies, Gino Cortopassi, Nipavan Chiamvimonvat, Donald M. Bers, Marcela Votruba, Anne A. Knowlton

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Mitochondrial fusion protein mutations are a cause of inherited neuropathies such as Charcot-Marie-Tooth disease and dominant optic atrophy. Previously we reported that the fusion protein optic atrophy 1 (OPA1) is decreased in heart failure. We investigated cardiac function, mitochondrial function, and mtDNA stability in a mouse model of the disease with OPA1 mutation. The homozygous mutation is embryonic lethal. Heterozygous OPA(+/-) mice exhibit reduced mtDNA copy number and decreased expression of nuclear antioxidant genes at 3 to 4 months. Although initial cardiac function was normal, at 12 months the OPA1(+/-) mouse hearts had decreased fractional shortening, cardiac output, and myocyte contraction. This coincided with the onset of blindness. In addition to small fragmented mitochondria, aged OPA1(+/-) mice had impaired cardiac mitochondrial function compared with wild-type littermates. OPA1 mutation leads to deficiency in antioxidant transcripts, increased reactive oxygen species, mitochondrial dysfunction, and late-onset cardiomyopathy.

Original languageEnglish (US)
JournalJournal of the American Heart Association
Volume1
Issue number5
DOIs
StatePublished - Oct 2012

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Autosomal Dominant Optic Atrophy
Cardiomyopathies
Mitochondrial DNA
Mutation
Antioxidants
Mitochondrial Dynamics
Charcot-Marie-Tooth Disease
Mitochondrial Proteins
Blindness
Cardiac Myocytes
Cardiac Output
Reactive Oxygen Species
Mitochondria
Heart Failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

OPA1 mutation and late-onset cardiomyopathy : mitochondrial dysfunction and mtDNA instability. / Chen, L.; Liu, Tingting; Tran, Alice; Lu, Xiyuan; Tomilov, Alexey A.; Davies, Vanessa; Cortopassi, Gino; Chiamvimonvat, Nipavan; Bers, Donald M.; Votruba, Marcela; Knowlton, Anne A.

In: Journal of the American Heart Association, Vol. 1, No. 5, 10.2012.

Research output: Contribution to journalArticle

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AU - Davies, Vanessa

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