Cardiac deficiency of single cytochrome oxidase assembly factor scox induces p53-dependent apoptosis in a Drosophila cardiomyopathy model

Human Molecular Genetics
Leticia Martínez-MorentinJuan J Arredondo

Abstract

The heart is a muscle with high energy demands. Hence, most patients with mitochondrial disease produced by defects in the oxidative phosphorylation (OXPHOS) system are susceptible to cardiac involvement. The presentation of mitochondrial cardiomyopathy includes hypertrophic, dilated and left ventricular noncompaction, but the molecular mechanisms involved in cardiac impairment are unknown. One of the most frequent OXPHOS defects in humans frequently associated with cardiomyopathy is cytochrome c oxidase (COX) deficiency caused by mutations in COX assembly factors such as Sco1 and Sco2. To investigate the molecular mechanisms that underlie the cardiomyopathy associated with Sco deficiency, we have heart specifically interfered scox expression, the single Drosophila Sco orthologue. Cardiac-specific knockdown of scox reduces fly lifespan, and it severely compromises heart function and structure, producing dilated cardiomyopathy. Cardiomyocytes with low levels of scox have a significant reduction in COX activity and they undergo a metabolic switch from OXPHOS to glycolysis, mimicking the clinical features found in patients harbouring Sco mutations. The major cardiac defects observed are produced by a significant increase in apopto...Continue Reading

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Citations

Dec 3, 2016·Heart Failure Reviews·Shasha ZhuWuzhou Yuan
Sep 28, 2017·Metallomics : Integrated Biometal Science·Zakery N BakerScot C Leary
Apr 4, 2021·Genes·Tingsen Benson LimChing Kit Chen
Nov 11, 2020·Biochimica Et Biophysica Acta. Bioenergetics·Michele Brischigliaro, Massimo Zeviani

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