title: cAMP regulates the functional activity, coupling efficiency and structural organization of mammalian FOF1 ATP synthase.
abstract: The present study shows that in isolated mitochondria and myoblast cultures depletion of cAMP, induced by sAC inhibition, depresses both ATP synthesis and hydrolysis by the FOF1 ATP synthase (complex V) of the oxidative phosphorylation system (OXPHOS). These effects are accompanied by the decrease of the respiratory membrane potential, decreased level of FOF1 connecting subunits and depressed oligomerization of the complex. All these effects of sAC inhibition are prevented by the addition of the membrane-permeant 8-Br-cAMP. These results show, for the first time, that cAMP promotes ATP production by complex V and prevents, at the same time, its detour to a mitochondrial membrane leak conductance, which is involved in cell death.
authors.affiliation: Institute of Biomembrane and Bioenergetics, National Research Council, Bari 70124, Italy. Electronic address: d.derasmo@ibbe.cnr.it.
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: Loris
authors.initials: L
authors.lastname: Micelli
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: Anna
authors.initials: A
authors.lastname: Signorile
authors.affiliation: Institute of Biomembrane and Bioenergetics, National Research Council, Bari 70124, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Lattanzio
authors.affiliation: Institute of Biomembrane and Bioenergetics, National Research Council, Bari 70124, Italy; Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Bari 70124, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Papa
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D053078:Membrane Potential, Mitochondrial; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases; D032446:Myoblasts / Q000378:metabolism; D010085:Oxidative Phosphorylation; D051381:Rats
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D000251:Adenosine Triphosphatases; D025261:Mitochondrial Proton-Translocating ATPases; D000262:Adenylyl Cyclases; C020439:oligomycin sensitivity-conferring protein
keywords: F(O)F(1) ATP synthase; Intramitochondrial cAMP; Mitochondria; sAC