Interaction of hormone-sensitive lipase with steroidogenic acute regulatory protein: facilitation of cholesterol transfer in adrenal.
Hormone-sensitive lipase (HSL) is responsible for the neutral cholesteryl ester hydrolase activity in steroidogenic tissues. Through its action, HSL is involved in regulating intracellular cholesterol metabolism and making unesterified cholesterol available for steroid hormone production. Steroidogenic acute regulatory protein (StAR) facilitates the movement of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane and is a critical regulatory step in steroidogenesis. In the current studies we demonstrate a direct interaction of HSL with StAR using in vitro glutathione S-transferase pull-down experiments. The 37-kDa StAR is coimmunoprecipitated with HSL from adrenals of animals treated with ACTH. Deletional mutations show that HSL interacts with the N-terminal as well as a central region of StAR. Coexpression of HSL and StAR in Chinese hamster ovary cells results in higher cholesteryl ester hydrolytic activity of HSL. Transient overexpression of HSL in Y1 adrenocortical cells increases mitochondrial cholesterol content under conditions in which StAR is induced. It is proposed that the interaction of HSL with StAR in cytosol increases the hydrolytic activity of HSL and that together HSL and StAR facilitate cholesterol movement from lipid droplets to mitochondria for steroidogenesis.
Shen
Wen-Jun
WJ
Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304-1290, USA.
Patel
Shailja
S
Natu
Vanita
V
Hong
Richard
R
Wang
Jenny
J
Azhar
Salman
S
Kraemer
Fredric B
FB
D000302:Adrenal Cortex / Q000166:cytology; D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002784:Cholesterol / Q000378:metabolism*; D006224:Cricetinae; D017353:Gene Deletion; D005982:Glutathione Transferase / Q000378:metabolism; D006868:Hydrolysis; D015151:Immunoblotting; D050356:Lipid Metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D002787:Sterol Esterase / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection; D000098682:Steroidogenic Acute Regulatory Protein
D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D000098682:Steroidogenic Acute Regulatory Protein; D002784:Cholesterol; D005982:Glutathione Transferase; D002787:Sterol Esterase