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Impaired ubiquitin‐proteasome‐mediated PGC ‐1α protein turnover and induced mitochondrial biogenesis secondary to complex‐ I deficiency
Author(s) -
Farhoud Murtada H.,
Nijtmans Leo G.,
Wanders Ronald J. A.,
Wessels Hans J. C. T.,
Lasonder Edwin,
Janssen Antoon J. M.,
Rodenburg Richard R. J.,
van den Heuvel Lambert P.,
Smeitink Jan A. M.
Publication year - 2012
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201100326
Subject(s) - mitochondrial biogenesis , proteasome , biogenesis , microbiology and biotechnology , mitochondrion , biology , activator (genetics) , regulator , protein turnover , ubiquitin , oxidative phosphorylation , nrf1 , proteomics , transcriptional regulation , oxidative stress , protein degradation , tfam , dnaja3 , gene expression , biochemistry , mitochondrial fusion , gene , protein biosynthesis , mitochondrial dna
Most eukaryotic cells depend on mitochondrial OX idative PHOS phorylation ( 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 PPAR γ co‐activator 1α ( PGC ‐1α) protein. Chronic oxidative stress suppresses the gene expression of PGC ‐1α 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.