title: Potential role of subunit c of F0F1-ATPase and subunit c of storage body in the mitochondrial permeability transition. Effect of the phosphorylation status of subunit c on pore opening.
abstract: Phosphorylated and non-phosphorylated forms of the F0F1-ATPase subunit c from rat liver mitochondria (RLM) were purified and their effect on the opening of the permeability transition pore (mPTP) was investigated. Addition of dephosphorylated subunit c to RLM induced mitochondrial swelling, decreased the membrane potential and reduced the Ca2+ uptake capacity, which was prevented by cyclosporin A. The same effect was observed in the presence of storage subunit c purified from livers of sheep affected with ceroid lipofuscinosis. In black-lipid bilayer membranes subunit c increased the conductance due to formation of single channels with fast and slow kinetics. The dephosphorylated subunit c formed channels with slow kinetics, i.e. the open state being of significantly longer duration than in the case of channels formed by the phosphorylated form that had short life spans and fast kinetics. The channels formed were cation-selective more so with the phosphorylated form. Subunit c of rat liver mitochondria was able to bind Ca2+. Collectively, the data allowed us to suppose that subunit c F0F1-ATPase might be a structural/regulatory component of mPTP exerting its role in dependence on phosphorylation status.
authors.affiliation: Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, Russia; Institute of Biomedicine, Biochemistry and Developmental Biology, University of Helsinki, Helsinki, Finland. Electronic address: tamara.azarashvili@gmail.com.
authors.forename: Tamara
authors.initials: T
authors.lastname: Azarashvili
authors.affiliation: Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, Russia; Institute of Biomedicine, Biochemistry and Developmental Biology, University of Helsinki, Helsinki, Finland.
authors.forename: Irina
authors.initials: I
authors.lastname: Odinokova
authors.affiliation: Institute for Biological Instrumentation, Russian Academy of Sciences, Pushchino, Moscow Region, Russia; San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Anush
authors.initials: A
authors.lastname: Bakunts
authors.affiliation: Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, Russia.
authors.forename: Vadim
authors.initials: V
authors.lastname: Ternovsky
authors.affiliation: Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, Russia.
authors.forename: Olga
authors.initials: O
authors.lastname: Krestinina
authors.affiliation: Institute of Biomedicine, Biochemistry and Developmental Biology, University of Helsinki, Helsinki, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Tyynelä
authors.affiliation: Institute of Biomedicine, Biochemistry and Developmental Biology, University of Helsinki, Helsinki, Finland; Department of Food and Environmental Sciences, University of Helsinki, P.O. Box 56, Viikki Biocenter 1, FIN-00014 Helsinki, Finland.
authors.forename: Nils-Erik Leo
authors.initials: NE
authors.lastname: Saris
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling / Q000187:drug effects; D010766:Phosphorylation; D011485:Protein Binding; D021122:Protein Subunits / Q000302:isolation & purification / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012756:Sheep
chemical_list: D008051:Lipid Bilayers; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D021122:Protein Subunits; D016572:Cyclosporine; D006180:Proton-Translocating ATPases; D002118:Calcium
keywords: Black-lipid membranes; F(0)F(1)-ATPase; Mitochondria; Permeability transition pore; Subunit c phosphorylation; [Ca(2+)]