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Impaired ubiquitin-proteasome-mediated PGC-1alpha protein turnover and induced mitochondrial biogenesis secondary to complex-I deficiency
- Source :
- Proteomics, 12, 9, pp. 1349-62, Proteomics, 12, 1349-62, Proteomics, 12(9), 1349-1362. Wiley-VCH Verlag
- Publication Year :
- 2012
-
Abstract
- Item does not contain fulltext 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. 01 mei 2012
- Subjects :
- Proteasome Endopeptidase Complex
Proteome
Genomic disorders and inherited multi-system disorders Energy and redox metabolism [IGMD 3]
Quantitative proteomics
Quality of nursing and allied health care [NCEBP 6]
Gene Expression
Oxidative phosphorylation
Biology
Real-Time Polymerase Chain Reaction
Biochemistry
Renal disorder Energy and redox metabolism [IGMD 9]
Oxidative Phosphorylation
Mitochondrial Proteins
Stable isotope labeling by amino acids in cell culture
Gene expression
Transcriptional regulation
Humans
Molecular Biology
Cells, Cultured
Heat-Shock Proteins
Electron Transport Complex I
Ubiquitin
Protein turnover
Mitochondrial medicine Energy and redox metabolism [IGMD 8]
Hydrogen Peroxide
Fibroblasts
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Cell biology
Mitochondria
Renal disorder Membrane transport and intracellular motility [IGMD 9]
Mitochondrial medicine [IGMD 8]
Proteasome
Mitochondrial biogenesis
Energy and redox metabolism Mitochondrial medicine [NCMLS 4]
Transcription Factors
Subjects
Details
- ISSN :
- 16159853
- Database :
- OpenAIRE
- Journal :
- Proteomics, 12, 9, pp. 1349-62, Proteomics, 12, 1349-62, Proteomics, 12(9), 1349-1362. Wiley-VCH Verlag
- Accession number :
- edsair.doi.dedup.....a8198477d09d46425e7d1eb702a73f67