M. Zizi et al., NADH REGULATES THE GATING OF VDAC, THE MITOCHONDRIAL OUTER-MEMBRANE CHANNEL, The Journal of biological chemistry, 269(3), 1994, pp. 1614-1616
Aerobic energy metabolism in cells involves the transfer of reducing e
quivalents from organic molecules to oxygen. NADH is important as a ca
rrier of these reducing equivalents and as a feedback regulator of gly
colysis. We report that micromolar quantities of NADH double the volta
ge dependence of the mitochondrial channel, VDAC, a critical pathway f
or the flux of metabolites between the cytoplasm and the mitochondrial
spaces. In the presence of NADH, the opening and closing of this chan
nel is more sensitive to changes in membrane potential and thus presum
ably better able to respond to changes in metabolic conditions. This e
ffect was observed both on a human and two fungal forms of VDAC, indic
ating a highly conserved regulatory mechanism. NAD+ and other nucleoti
des tested failed to mimic the action of NADH. This ability of NADH to
facilitate VDAC closure could be one mechanism by which glycolysis ca
n suppress oxidative phosphorylation (Crabtree effect).