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003			PC16833
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008			220505b xxu||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_93033 _aCervera, Margarita _eInstituto de Investigación imas12
100			_93034 _aArredondo Juan J, _eInstituto de Investigación imas12
245	0	0	_aCardiac deficiency of single cytochrome oxidase assembly factor scox induces p53-dependent apoptosis in a Drosophila cardiomyopathy model. _h[artículo]
260			_bHuman molecular genetics, _c2015
300			_a24(13):3608-22.
500			_aFormato Vancouver: Martínez Morentín L, Martínez L, Piloto S, Yang H, Schon EA, Garesse R et al. Cardiac deficiency of single cytochrome oxidase assembly factor scox induces p53-dependent apoptosis in a Drosophila cardiomyopathy model. Hum Mol Genet. 2015 Jul 1;24(13):3608-22.
501			_aPMID: 25792727 PMCID: PMC4459388.
504			_aContiene 72 referencias
520			_aThe 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 apoptosis, which is dp53-dependent. Genetic and molecular evidence strongly suggest that dp53 is directly involved in the development of the cardiomyopathy induced by scox deficiency. Remarkably, apoptosis is enhanced in the muscle and liver of Sco2 knock-out mice, clearly suggesting that cell death is a key feature of the COX deficiencies produced by mutations in Sco genes in humans.
710			_9625 _aInstituto de Investigación imas12
856			_uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459388/ _yAcceso libre
942			_2ddc _cART _n0