The ectopic FOF1 ATP synthase of rat liver is modulated in acute cholestasis by the inhibitor protein IF1

Rat liver plasma membranes contain FOF1 complexes (ecto-FOF1) displaying a similar molecular weight to the mitochondrial FOF1 ATP synthase, as evidenced by Blue Native PAGE. Their ATPase activity was stably reduced in short-term extra-hepatic cholestasis. Immunoblotting and immunoprecipitation analyses demonstrated that the reduction in activity was not due to a decreased expression of ecto-FOF1 complexes, but to an increased level of an inhibitory protein, ecto-IF1, bound to ecto-FOF1. Since cholestasis down regulates the hepatic uptake of HDL-cholesterol, and ecto-FOF1 has been shown to mediate SR-BI-independent hepatic uptake of HDL-cholesterol, these findings provide support to the hypothesis that ecto-FOF1 contributes to the fine control of reverse cholesterol transport, in parallel with SR-BI. No activity change of the mitochondrial FOF1 ATP synthase (m-FOF1), or any variation of its association with m-IF1 was observed in cholestasis, indicating that ecto-IF1 expression level is modulated independently from that of ecto-FOF1, m-IF1 and m-FOF1.