Porin and cytochrome oxidase containing contact sites involved in the oxidation of cytosolic NADH.
Cytochrome c (cyto-c) added to isolated mitochondria promotes the oxidation of extra-mitochondrial NADH and the reduction of molecular oxygen associated to the generation of an electrochemical membrane potential available for ATP synthesis. The electron transport pathway activated by exogenous cyto-c molecules is completely distinct from the one catalyzed by the respiratory chain. Dextran sulfate (500 kDa), known to interact with porin (the voltage-dependent anion channel), other than to inhibit the release of ATP synthesized inside the mitochondria, greatly decreases the activity of exogenous NADH/cyto-c system of intact mitochondria but has no effect on the reconstituted system made of mitoplasts and external membrane preparations. The results obtained are consistent with the existence of specific contact sites containing cytochrome oxidase and porin, as components of the inner and the outer membrane respectively, involved in the oxidation of cytosolic NADH. The proposal is put forward that the bi-trans-membrane electron transport chain activated by cytosolic cyto-c becomes, in physio-pathological conditions: (i) functional in removing the excess of cytosolic NADH; (ii) essential for cell survival in the presence of an impairment of the first three respiratory complexes; and (iii) an additional source of energy at the beginning of apoptosis.
La Piana
Gianluigi
G
Department of Biochemistry and Molecular Biology, University of Bari, via Orabona 4, 70126 Bari, Italy.
Marzulli
Domenico
D
Gorgoglione
Vincenza
V
Lofrumento
Nicola Elio
NE
D000255:Adenosine Triphosphate / Q000378:metabolism; D001665:Binding Sites; D002468:Cell Physiological Phenomena; D003574:Cytochrome c Group / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D016264:Dextran Sulfate / Q000494:pharmacology; D004563:Electrochemistry; D004579:Electron Transport / Q000187:drug effects; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism* / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D018272:Porins / Q000378:metabolism* / Q000494:pharmacology
D003574:Cytochrome c Group; D018272:Porins; D009243:NAD; D000255:Adenosine Triphosphate; D016264:Dextran Sulfate; D003576:Electron Transport Complex IV; D014450:Electron Transport Complex III; D010100:Oxygen