Nigericin inhibits accumulation of the steroidogenic acute regulatory protein but not steroidogenesis

The steroidogenic acute regulatory (StAR) protein mediates the delivery of cholesterol from the outer to the inner mitochondrial membrane, where the c holesterol side chain cleavage complex converts it to pregnenolone. While t he mechanism by which this mitochondrial protein acts is poorly understood. one component of the mitochondrial electrochemical gradient, the electroch emical potential (Delta psi), appears to be essential. In this study, the i mportance of the other component, the proton gradient (Delta pH), was exami ned. Disruption of Delta pH with the electroneutral K+/H+ exchanger, nigeri cin, had no effect on steroidogenesis in MA-10 mouse Leydig tumor cells at concentrations which significantly reduced StAR protein levels. These data indicate for the first time in true steroidogenic cells, that StAR can act prior to being fully imported into the mitochondria and are consistent with observations made in COS-1 cells using mutant Forms of StAR. These results support the hypothesis that a Delta psi-dependent factor is required for S tAR activity and demonstrate that nigericin is the first compound described . capable of inhibiting StAR accumulation without affecting steroidogenesis . (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.