title: Effects of extramitochondrial ADP on permeability transition of mouse liver mitochondria.
abstract: Carboxyatractylate (CAT) and atractylate inhibit the mitochondrial adenine nucleotide translocator (ANT) and stimulate the opening of permeability transition pore (PTP). Following pretreatment of mouse liver mitochondria with 5 microM CAT and 75 microM Ca2+, the activity of PTP increased, but addition of 2 mM ADP inhibited the swelling of mitochondria. Extramitochondrial Ca2+ concentration measured with Calcium-Green 5N evidenced that 2 mM ADP did not remarkably decrease the free Ca2+ but the release of Ca2+ from loaded mitochondria was stopped effectively after addition of 2 mM ADP. CAT caused a remarkable decrease of the maximum amount of calcium ions, which can be accumulated by mitochondria. Addition of 2 mM ADP after 5 microM CAT did not change the respiration, but increased the mitochondrial capacity for Ca2+ at more than five times. Bongkrekic acid (BA) had a biphasic effect on PT. In the first minutes 5 microM BA increased the stability of mitochondrial membrane followed by a pronounced opening of PTP too. BA abolished the action about of 1 mM ADP, but was not able to induce swelling of mitochondria in the presence of 2 mM ADP. We conclude that the outer side of inner mitochondrial membrane has a low affinity sensor for ADP, modifying the activity of PTP. The pathophysiological importance of this process could be an endogenous prevention of PT at conditions of energetic depression.
authors.affiliation: Muskellabor der Neurologischen Klinik der Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Str. 40, D-06097 Halle (Saale), Germany. zemfira.gizatullina@rambler.ru
authors.forename: Zemfira Z
authors.initials: ZZ
authors.lastname: Gizatullina
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Stephan
authors.initials: S
authors.lastname: Zierz
authors.forename: Frank Norbert
authors.initials: FN
authors.lastname: Gellerich
mesh_terms: D033781:Adenine Nucleotide Translocator 3 / Q000037:antagonists & inhibitors; D000244:Adenosine Diphosphate / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives* / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001865:Bongkrekic Acid / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D010539:Permeability / Q000187:drug effects; D018272:Porins / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
chemical_list: D033781:Adenine Nucleotide Translocator 3; D018272:Porins; D001865:Bongkrekic Acid; D001278:Atractyloside; D000244:Adenosine Diphosphate; C003853:carboxyatractyloside; D002118:Calcium