Sr. King et al., Nigericin inhibits accumulation of the steroidogenic acute regulatory protein but not steroidogenesis, MOL C ENDOC, 166(2), 2000, pp. 147-153
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.