The ectopic F(O)F(1) ATP synthase of rat liver is modulated in acute cholestasis by the inhibitor protein IF1.
Rat liver plasma membranes contain F(O)F(1) complexes (ecto-F(O)F(1)) displaying a similar molecular weight to the mitochondrial F(O)F(1) 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-F(O)F(1) complexes, but to an increased level of an inhibitory protein, ecto-IF(1), bound to ecto-F(O)F(1). Since cholestasis down regulates the hepatic uptake of HDL-cholesterol, and ecto-F(O)F(1) has been shown to mediate SR-BI-independent hepatic uptake of HDL-cholesterol, these findings provide support to the hypothesis that ecto-F(O)F(1) contributes to the fine control of reverse cholesterol transport, in parallel with SR-BI. No activity change of the mitochondrial F(O)F(1) ATP synthase (m-F(O)F(1)), or any variation of its association with m-IF(1) was observed in cholestasis, indicating that ecto-IF(1) expression level is modulated independently from that of ecto-F(O)F(1), m-IF(1) and m-F(O)F(1).
Giorgio
Valentina
V
Department of Biomedical Sciences and Technologies, University of Udine, p.le Kolbe 4, I-33100, Udine, Italy.
Bisetto
Elena
E
Franca
Raffaella
R
Harris
David A
DA
Passamonti
Sabina
S
Lippe
Giovanna
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002779:Cholestasis / Q000201:enzymology*; D008076:Cholesterol, HDL / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006868:Hydrolysis; D015151:Immunoblotting; D047468:Immunoprecipitation; D008099:Liver / Q000201:enzymology*; D008297:Male; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000097795:ATPase Inhibitory Protein
D000255:Adenosine Triphosphate; D008076:Cholesterol, HDL; D011506:Proteins; D006180:Proton-Translocating ATPases; D000097795:ATPase Inhibitory Protein