NADH regulates the gating of VDAC, the mitochondrial outer membrane channel.
Aerobic energy metabolism in cells involves the transfer of reducing equivalents from organic molecules to oxygen. NADH is important as a carrier of these reducing equivalents and as a feedback regulator of glycolysis. We report that micromolar quantities of NADH double the voltage dependence of the mitochondrial channel, VDAC, a critical pathway for the flux of metabolites between the cytoplasm and the mitochondrial spaces. In the presence of NADH, the opening and closing of this channel is more sensitive to changes in membrane potential and thus presumably better able to respond to changes in metabolic conditions. This effect was observed both on a human and two fungal forms of VDAC, indicating a highly conserved regulatory mechanism. NAD+ and other nucleotides tested failed to mimic the action of NADH. This ability of NADH to facilitate VDAC closure could be one mechanism by which glycolysis can suppress oxidative phosphorylation (Crabtree effect).
Zizi
M
M
Department of Zoology, University of Maryland, College Park 20742.
Forte
M
M
Blachly-Dyson
E
E
Colombini
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D017124:Conserved Sequence; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism* / Q000494:pharmacology; D009492:Neurospora crassa / Q000378:metabolism*; D010084:Oxidation-Reduction; D018272:Porins; D011336:Probability; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D050994:Voltage-Dependent Anion Channels
D007473:Ion Channels; D008565:Membrane Proteins; D018272:Porins; D050994:Voltage-Dependent Anion Channels; D009243:NAD