THE ROLE OF PYRIDINE DINUCLEOTIDES IN REGULATING THE PERMEABILITY OF THE MITOCHONDRIAL OUTER-MEMBRANE

Both NADH and NADPH reduce the permeability of the mitochondrial outer membrane to ADP. This is specific for the outer membrane and uncorrel ated with the respiratory control ratio, This could result in a 7-fold difference between the concentration of ADP in the intermembrane spac e and that in the external environment, (at 5 mu M ADP). in both cases the permeability declines by a factor of 5, but NADH is more potent: K-D = 86 mu M for NADH versus 580 mu M for NADPH. The lower apparent a ffinity for NADPH is partly explained by Mg2+-NADPH being the active s pecies, and under our conditions only 30% of the NADPH is in this form . The corrected K-D is 184 mu M. Free NADH has the same charge as the Mg2+-NADPH complex, and thus both likely bind to the same site, The ab ility of NADH and NADPH to induce the closure of reconstituted VDAC ch annels is consistent with VDAC being the main pathway for metabolite f low across the outer membrane, Oncotic pressure, effective at inducing VDAC closure, also decreases the enter membrane permeability. Thus, i n the presence of cytosolic colloidal osmotic pressure NAD(P)H may inh ibit mitochondrial catabolic pathways and divert reducing equivalents to anabolic pathways.