Chen, L., Liu, T., Tran, A., Lu, X., Tomilov, A. A., Davies, V., Cortopassi, G., Chiamvimonvat, N, Bers, D. M., Votruba, Marcela  ORCID: https://orcid.org/0000-0002-7680-9135 and Knowlton, A. A.
2012.
OPA1 mutation and late-onset cardiomyopathy: Mitochondrial dysfunction and mtDNA instability.
Journal of the American Heart Association
, e003012.
10.1161/JAHA.112.003012
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Abstract
BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: OPA1 mutation leads to deficiency in antioxidant transcripts, increased reactive oxygen species, mitochondrial dysfunction, and late-onset cardiomyopathy.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Optometry and Vision Sciences Research Institutes & Centres > Neuroscience and Mental Health Research Institute (NMHII) |
| Subjects: | R Medicine > RC Internal medicine R Medicine > RE Ophthalmology |
| Additional Information: | Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/2047-9980/ (accessed 25/02/2014). |
| Publisher: | American Heart Association |
| ISSN: | 0041-008X |
| Date of First Compliant Deposit: | 30 March 2016 |
| Last Modified: | 12 May 2023 21:23 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/43741 |
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