Impaired ubiquitin-proteasome-mediated PGC-1alpha protein turnover and induced mitochondrial biogenesis secondary to complex-I deficiency.
SourceProteomics, 12, 9, (2012), pp. 1349-1362
1 mei 2012
Article / Letter to editor
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Paediatrics - OUD tm 2017
Laboratory of Genetic, Endocrine and Metabolic Diseases
SubjectIGMD 3: Genomic disorders and inherited multi-system disorders NCMLS 4: Energy and redox metabolism; IGMD 8: Mitochondrial medicine; IGMD 8: Mitochondrial medicine NCMLS 4: Energy and redox metabolism; IGMD 9: Renal disorder NCMLS 4: Energy and redox metabolism; IGMD 9: Renal disorder NCMLS 5: Membrane transport and intracellular motility; NCEBP 6: Quality of nursing and allied health care; NCMLS 4: Energy and redox metabolism IGMD 8: Mitochondrial medicine; IGMD 8: Mitochondrial medicine NCMLS 4: Energy and redox metabolism; IGMD 9: Renal disorder NCMLS 5: Membrane transport and intracellular motility
Most eukaryotic cells depend on mitochondrial OXidative PHOSphorylation (OXPHOS) in their ATP supply. The cellular consequences of OXPHOS defects and the pathophysiological mechanisms in related disorders are incompletely understood. Using a quantitative proteomics approach we provide evidence that a genetic defect of complex-I of the OXPHOS system may associate with transcriptional derangements of mitochondrial biogenesis through stabilization of the master transcriptional regulator PPARgamma co-activator 1alpha (PGC-1alpha) protein. Chronic oxidative stress suppresses the gene expression of PGC-1alpha but concomitant inhibition of the ubiquitin-proteasome system (UPS) can stabilize this co-activator protein, thereby inducing its downstream metabolic gene expression programs. Thus, mitochondrial biogenesis, which lays at the heart of the homeostatic control of energy metabolism, can be deregulated by secondary impairments of the protein turnover machinery.
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