Regulation of the biogenesis of OXPHOS complexes in cell transition from replicating to quiescent state Involvement of PKA and effect of hydroxytyrosol

A study is presented on the expression of mitochondria] oxidative phosphorylation complexes in exponentially growing and serum-starved, quiescent human fibroblast cultures. The functional levels of respiratory complexes land ill 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-1 alpha) 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-l alpha gene, was found. Hydroxytyrosol prevented the decline in the expression of the PGC-la 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-1a in the regulation of OXPHOS in cell transition from the replicating to the quiescent state. (c) 2014 Elsevier B.V. All rights reserved,