Beta-NADH decreases the permeability of the mitochondrial outer membrane to ADP by a factor of 6.
Mitochondria with intact outer membrane (99% intact based on cytochrome c impermeability) were isolated and used to measure the permeability of their outer membrane to ADP. beta-NADH reduced the permeability in a concentration-dependent manner (KD = 87 +/- 5 microM) by a factor of 6. alpha-NADH and beta-NAD+ cannot mimic the action of beta-NADH. The mitochondrial outer membranes become rate-limiting in the presence of beta-NADH at low, physiologically relevant, ADP concentrations (< 30 microM). beta-NADH has been shown to increase the voltage dependence of VDAC (a major pathway for metabolite transport across the outer membrane) in a reconstituted system and this may be the way it acts on the isolated mitochondria. Inhibition of beta-NADH dehydrogenases does not inhibit the action of beta-NADH indicating that it is not acting by delivering reducing equivalents. The ability of beta-NADH, produced by glycolysis, to inhibit mitochondrial function by reducing the permeability of the outer membrane may be one pathway responsible for the Crabtree effect.
Lee
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AC
Department of Zoology, University of Maryland, College Park 20742.
Zizi
M
M
Colombini
M
M
D000244:Adenosine Diphosphate / Q000378:metabolism*; D001692:Biological Transport; D007425:Intracellular Membranes / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010539:Permeability; D011198:Solanum tuberosum
D009243:NAD; D000244:Adenosine Diphosphate; D010100:Oxygen