title: Regulation of the biogenesis of OXPHOS complexes in cell transition from replicating to quiescent state: involvement of PKA and effect of hydroxytyrosol.
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.
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Bari 70124,Italy. Electronic address: anna.signorile@uniba.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Signorile
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Bari 70124,Italy.
authors.forename: Loris
authors.initials: L
authors.lastname: Micelli
authors.affiliation: Institute of Biomembrane and Bioenergetics, CNR, Bari, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: De Rasmo
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Bari 70124,Italy.
authors.forename: Arcangela
authors.initials: A
authors.lastname: Santeramo
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Bari 70124,Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Papa
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Bari 70124,Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Ficarella
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Bari 70124,Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Gattoni
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Bari 70124,Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Scacco
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Bari 70124,Italy; Institute of Biomembrane and Bioenergetics, CNR, Bari, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Papa
mesh_terms: D025181:ATP Synthetase Complexes / Q000235:genetics; D000255:Adenosine Triphosphate / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis* / Q000378:metabolism; D042967:Electron Transport Complex I / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D051266:Nuclear Respiratory Factor 1 / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D051266:Nuclear Respiratory Factor 1; D047492:Peroxisome Proliferator-Activated Receptors; C005975:3,4-dihydroxyphenylethanol; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D017868:Cyclic AMP-Dependent Protein Kinases; D025181:ATP Synthetase Complexes; D042967:Electron Transport Complex I; D010626:Phenylethyl Alcohol
keywords: CREB; Hydroxytyrosol; Mitochondria; PGC-1α; PKA; Quiescent fibroblasts