1. Regulation of the biogenesis of OXPHOS complexes in cell transition from replicating to quiescent state: involvement of PKA and effect of hydroxytyrosol
- Author
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Anna, Signorile, Loris, Micelli, Domenico, De Rasmo, Arcangela, Santeramo, Francesco, Papa, Romina, Ficarella, Giuliano, Gattoni, Salvatore, Scacco, and Sergio, Papa
- Subjects
Electron Transport Complex I ,Nuclear Respiratory Factor 1 ,Peroxisome Proliferator-Activated Receptors ,Hydrogen Peroxide ,Fibroblasts ,Phenylethyl Alcohol ,Cyclic AMP-Dependent Protein Kinases ,Oxidative Phosphorylation ,Mitochondria ,ATP Synthetase Complexes ,Adenosine Triphosphate ,Humans ,Cyclic AMP Response Element-Binding Protein ,Signal Transduction - Abstract
A study is presented on the expression of mitochondrial oxidative phosphorylation complexes in exponentially growing and serum-starved, quiescent human fibroblast cultures. The functional levels of respiratory complexes I and III and complex V (adenosine triphosphate (ATP) synthase) were found to be severely depressed in serum-starved fibroblasts. The depression of oxidative phosphorylation system (OXPHOS) complexes was associated with reduced levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and the down-stream nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factors (TFAM). In serum-starved fibroblasts decrease of the catalytic activity of AMP cyclic dependent protein kinase (PKA) and phosphorylation of cAMP response element-binding protein (CREB), the transcription coactivator of the PGC-1α gene, was found. Hydroxytyrosol prevented the decline in the expression of the PGC-1α transcription cascade of OXPHOS complexes in serum-starved fibroblast cultures. The positive effect of HT was associated with activation of PKA and CREB phosphorylation. These results show involvement of PKA, CREB and PGC-1α in the regulation of OXPHOS in cell transition from the replicating to the quiescent state.
- Published
- 2013