Interaction of Hormone-sensitive Lipase with Steroidogeneic Acute Regulatory Protein

Abstract

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. 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. Neutral cholesteryl ester hydrolase activity can be demonstrated in most cells, including adipose tissue, adrenal, testes, placenta, macrophages, heart, skeletal and smooth muscles; steroidogenic tissues are especially enriched in this activity (1Kraemer F.B. Shen W.-J. J. Lipid Res. 2002; 43: 1585-1594Abstract Full Text Full Text PDF PubMed Scopus (375) Google Scholar). Several lines of evidence suggest that hormone-sensitive lipase (HSL) 1The abbreviations used are: HSL, hormone-sensitive lipase; ALBP, adipocyte lipid-binding protein; Bt2cAMP, dibutyryl cAMP; CHO, Chinese hamster ovary; CMV, cytomegalovirus; GST, glutathione S-transferase; HDL3, human high density lipoprotein3; LDL, low density lipoprotein; StAR, steroidogenic acute regulatory protein; START domain, StAR-related lipid transfer domain; TGH, triacylglycerol hydrolase. is responsible for the neutral cholesteryl ester hydrolase activity in steroidogenic tissues. The most direct and convincing evidence comes from HSL knockout mice, where no detectable HSL protein and no neutral cholesteryl ester hydrolase activity are observed in the adrenal (2Kraemer F.B. Shen W.-J. Natu V. Patel S. Osuga J.-i. Ishibashi S. Azhar S. Endocrinology. 2002; 143: 801-806Crossref PubMed Scopus (51) Google Scholar) or testis (3Osuga J.-i. Ishibashi S. Oka T. Yagyu H. Tozawa R. Fujimoto A. Shionoira F. Yahagi N. Kraemer F.B. Tsutsumi O. Yamada N. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 787-792Crossref PubMed Scopus (503) Google Scholar). It is believed that through its action as a neutral cholesteryl ester hydrolase, HSL is involved in regulating intracellular cholesterol metabolism and, thus, contributing to a variety of pathways in which cells utilize cholesterol. The primary amino acid sequence of HSL is unrelated to any of the other known mammalian lipases; however, it shares some sequence similarity with liver arylacetamide deacetylase within its catalytic domain (4Probst M.R. Beer M. Beer D. Jenö D. Meter U.A. Randolfo G. J. Biol. Chem. 1994; 269: 21650-21656Abstract Full Text PDF PubMed Google Scholar). The C-terminal portion of HSL displays secondary structural homology with that of acetylcholinesterase and several fungal lipases (5Contreras J.A. Karlsson M. Østerlund T. Laurell H. Svensson A. Holm C. J. Biol. Chem. 1996; 271: 31426-31430Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar) and bacterial brefeldin A esterase (6Wei Y. Contreras J.A. Sheffield P. Osterlund T. Derewenda U. Kneusel R.E. Matern U. Holm C. Derewenda Z.S. Nat. Struct. Biol. 1999; 6: 340-345Crossref PubMed Scopus (147) Google Scholar), consisting of parallel β-sheets flanked by α-helical connections, which has allowed these proteins to be classified as α/β-hydrolases (7Ollis D.L. Cheah E. Cygler M. Dijkstra B. Frolow F. Franken S.M. Harel M. Remington S.J. Silman I. Schrag J. Protein Eng. 1992; 5: 197-211Crossref PubMed Scopus (1845) Google Scholar). Using limited proteolysis, it has been suggested that HSL is composed of two major structural domains (8Østerlund T. Danielsson B. Degerman E. Contreras J.A. Edgren G. Davis R.C. Schotz M.C. Holm C. Biochem. J. 1996; 319: 411-420Crossref PubMed Scopus (138) Google Scholar, 9Østerlund T. Beussman D.J. Julenius K. Poon P.H. Linse S. Shabanowitz J. Hunt D.F. Schotz M.C. Derewenda Z.S. Holm C. J. Biol. Chem. 1999; 274: 15382-15388Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar). Based on sequence alignment, structural homology with fungal lipases, and mutational analyses, the C-terminal domain has been shown to contain the catalytic triad and other residues important in hydrolytic activity, as well as a 150-amino acid insert that has been termed the regulatory module because several serines located within this region have been shown to be phosphorylated (1Kraemer F.B. Shen W.-J. J. Lipid Res. 2002; 43: 1585-1594Abstract Full Text Full Text PDF PubMed Scopus (375) Google Scholar, 10Østerlund T. Eur. J. Biochem. 2001; 268: 1899-1907Crossref PubMed Scopus (58) Google Scholar). The N-terminal domain in rat HSL constitutes the first 323 amino acids, which are encoded by exons 1–4, and displays no sequence or structural similarity with any other known proteins (8Østerlund T. Danielsson B. Degerman E. Contreras J.A. Edgren G. Davis R.C. Schotz M.C. Holm C. Biochem. J. 1996; 319: 411-420Crossref PubMed Scopus (138) Google Scholar, 9Østerlund T. Beussman D.J. Julenius K. Poon P.H. Linse S. Shabanowitz J. Hunt D.F. Schotz M.C. Derewenda Z.S. Holm C. J. Biol. Chem. 1999; 274: 15382-15388Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar). We (11Shen W.-J. Sridhar K. Bernlohr D.A. Kraemer F.B. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 5528-5532Crossref PubMed Scopus (182) Google Scholar) and others (12Syu L.-J. Saltiel A.R. Mol. Cell. 1999; 4: 109-115Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar) have shown that HSL interacts specifically with intracellular proteins in adipose tissue. The interaction of HSL with adipocyte lipid-binding protein (ALBP) occurs through amino acid residues within the N-terminal domain; the physical interaction of ALBP with HSL increases the hydrolytic activity of HSL and protects HSL from product inhibition by fatty acids (13Shen W.-J. Liang Y. Hong R. Patel S. Natu V. Sridhar K. Jenkins A. Bernlohr D.A. Kraemer F.B. J. Biol. Chem. 2001; 276: 49443-49448Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar). In the same way that the interaction of HSL with ALBP might help to facilitate the trafficking of fatty acids in adipose cells, HSL might interact with specific cholesterol carrier proteins in the adrenal and, thus, facilitate intracellular cholesterol trafficking to mitochondria for steroidogenesis. The steroidogenic acute regulatory protein (StAR) is synthesized as a 37-kDa protein that is targeted to and processed in mitochondria to a 30-kDa mature protein that facilitates the movement of cholesterol from the outer mitochondrial membrane to the cholesterol side chain cleavage enzyme (CYP11A1) on the inner mitochondrial membrane (14Miller W.L. Strauss III, J.F. J. Steroid Biochem. Mol. Biol. 1999; 69: 131-141Crossref PubMed Scopus (145) Google Scholar, 15Stocco D.M. Annu. Rev. Physiol. 2001; 63: 193-213Crossref PubMed Scopus (695) Google Scholar). Identification of mutations in humans (16Bose H.S. Sugawara T. Strauss III, J.F. Miller W.L. N. Engl. J. Med. 1996; 335: 1870-1878Crossref PubMed Scopus (525) Google Scholar) and mouse knockout experiments (17Caron K.M. Soo S.C. Wetsel W.C. Stocco D.M. Clark B.J. Parker K.L. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 11540-11545Crossref PubMed Scopus (382) Google Scholar) have implicated StAR as a critical regulatory step in steroidogenesis. StAR has been shown to possess sterol transfer activity in vitro (18Kallen C.B. Billheimer J.T. Summers S.A. Stayrook S.E. Lewis M. Strauss III, J.F. J. Biol. Chem. 1998; 273: 26285-26288Abstract Full Text Full Text PDF PubMed Scopus (177) Google Scholar, 19Petrescu A.D. Gallegos A.M. Okamura Y. Strauss III, J.F. Schroeder F. J. Biol. Chem. 2001; 276: 36970-36982Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar). The crystal structure of StAR shows that it has a classic lipid transporter-like structure (20Tsujishita Y. Hurley J.H. Nat. Struct. Biol. 2000; 7: 408-414Crossref PubMed Scopus (446) Google Scholar, 21Romanowski M.J. Soccio R.E. Breslow J.L. Burley S.K. Proc. Natl. Acad. Sci. U. S. A. 2002; 99: 6949-6954Crossref PubMed Scopus (141) Google Scholar), which is characterized by internal hydrophobic cavities, clefs, or tunnels. In this paper, we demonstrate a direct interaction of HSL with StAR in both in vitro and in vivo physiological conditions. HSL interacts with the N-terminal as well as a central region of StAR. Coexpression of HSL and StAR in CHO cells results in higher 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 stored lipid droplets to mitochondria for steroidogenesis. Chemicals and Reagents—Reagents were obtained from the following sources. Bovine serum albumin (fraction V) was from Intergen Co., Purchase, NY. Fetal bovine serum was from Gemini Bio-Products, Inc., Calabasas, CA. Coon's F-12/Dulbecco's modified Eagle's media and Lipofectin reagent were from Invitrogen. ECL Western blotting detection reagents, horseradish peroxidase-linked whole antibody anti-rabbit IgG, GST-glutathione agarose beads, [35S]methionine, and cholesteryl [1-14C]oleate were from Amersham Biosciences. Protein reagent was from was from The was from cells, cells, transfer and were from was from CA. The was from CA. were from J. T. were from human high density was and characterized as E. Azhar S. J. Biol. Chem. Full Text PDF PubMed Google Scholar). Deletional and of was used to from the as well as of StAR from J. III, of the StAR C-terminal the was the and the StAR StAR StAR StAR StAR the N-terminal the the of StAR and a The StAR StAR StAR StAR StAR The of the N-terminal were the and of StAR the internal of StAR were by the internal and The used for the StAR the internal was The StAR StAR StAR The in which amino acids were from StAR was with the using the following and The of the were by using In sequence of the StAR the StAR were in vitro with using the and protein were as (11Shen W.-J. Sridhar K. Bernlohr D.A. Kraemer F.B. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 5528-5532Crossref PubMed Scopus (182) Google Scholar). or was with in a the were in and with StAR a the were in and proteins that to the were in on in and using a and were with or and the adrenals and the were in and with and and for The was used for and protein of HSL was as (11Shen W.-J. Sridhar K. Bernlohr D.A. Kraemer F.B. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 5528-5532Crossref PubMed Scopus (182) Google Scholar). A was with protein A and with consisting of protein and protein A. the was for and in with bovine serum albumin and in The was in with and for on to paper, and with from J. and cells were in modified Eagle's with serum under cells were a density of in well the to with of or StAR of and of in of Lipofectin reagent following the from the were for of HSL adrenocortical cells were in with bovine and under cells were a density in the to was with of or from of using Lipofectin cells were in serum with of and for were to with bovine serum albumin and with in the of for in of cells were as M.J. C. J. Biol. Chem. Full Text PDF PubMed Google Scholar) with some cells were for and with The was in a with and cells were allowed to for the cells were with several in a and were to of and to of the were for cholesterol and protein the mitochondrial the were for and the were for The the mitochondrial was in mitochondrial and of ester and cholesterol content were using the cholesterol from by from mitochondrial were by the of and J. Biochem. Physiol. PubMed Scopus Google Scholar). the was and in of was to and with to and acid to and cholesteryl ester were on a on the The cholesterol and cholesteryl ester were by to and as (2Kraemer F.B. Shen W.-J. Natu V. Patel S. Osuga J.-i. Ishibashi S. Azhar S. Endocrinology. 2002; 143: 801-806Crossref PubMed Scopus (51) Google Scholar). of HSL activity was using a cholesteryl as M. Kraemer F.B. R. Mol. Google Scholar). Protein was using protein was in as (11Shen W.-J. Sridhar K. Bernlohr D.A. Kraemer F.B. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 5528-5532Crossref PubMed Scopus (182) Google Scholar). are as the S.E. were by using for HSL with StAR in HSL might interact with StAR, StAR that was by in vitro was with rat or with The was with beads, and the proteins that to the were and on and are shown in protein to interact with StAR, was to StAR. these results suggest that HSL is of specifically with StAR in HSL with StAR in that the interaction of HSL with StAR occurs in were with to StAR or with The adrenals were and the and HSL was from of the adrenals with The were on and with shown in StAR in of adrenals as a 30-kDa the mature protein its in the 30-kDa StAR is in the with from adrenal to interaction of HSL with StAR in of the 37-kDa StAR, which is the product synthesized in the to and in mitochondria to the 30-kDa is in the of adrenal with the interaction of HSL with StAR in the 37-kDa product is no the of the 37-kDa StAR In adrenal tissues with have any detectable StAR, that StAR was in the because of the The in the with that are by the The in the with because consisting of to protein A was used which from in the the is of StAR in the with the structural in StAR that are its interaction with HSL, a of C-terminal StAR StAR StAR StAR and StAR was and the of these in vitro with HSL were of the with were specifically by that the N-terminal amino acids of StAR, which the that StAR to the mitochondria and which is in the can in the interaction with HSL. In of the of the 30-kDa StAR to be coimmunoprecipitated with HSL, it is that in to the of the protein be involved in the interaction with HSL. a of N-terminal of StAR was and to interact with HSL the first amino acids of StAR its to be by that the is the region in the interaction with HSL. the first amino acids of StAR its to be by however, N-terminal of the first and amino acids the and N-terminal were StAR and StAR to to however, StAR it that within the first acid and within the region amino acids and are to the interaction of StAR with of HSL with N-terminal StAR N-terminal of StAR were as under was in vitro and with or and and and and were in vitro and with and or and as in of HSL with and C-terminal StAR StAR and StAR and and StAR and were in vitro and with and or and as in StAR HSL interaction of ALBP with HSL is to the hydrolytic activity of the enzyme (13Shen W.-J. Liang Y. Hong R. Patel S. Natu V. Sridhar K. Jenkins A. Bernlohr D.A. Kraemer F.B. J. Biol. Chem. 2001; 276: 49443-49448Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar). The of ALBP to by HSL is to the and of fatty acids by ALBP is on the physical interaction of ALBP with HSL, that the interaction a or on the StAR is known to possess fatty acid the that StAR interact with HSL the that the interaction of StAR with HSL might HSL hydrolytic this HSL was in CHO cells, and hydrolytic activity cholesteryl ester was of StAR or The of HSL under these conditions was as by Coexpression of HSL and StAR in of cholesteryl ester as observed with ALBP, the interaction of StAR with HSL can the hydrolytic activity of the is a interaction in vitro and HSL of StAR were with HSL in CHO cells, and hydrolytic activity cholesteryl ester was of the first or amino acids of StAR, that HSL, hydrolytic activity cholesteryl ester to to that of StAR of the first amino acids of StAR to HSL activity, this of the first amino acids, a that HSL, no on HSL of StAR which HSL, HSL that HSL and no on HSL a in which amino acids were from StAR to HSL hydrolytic it that the of StAR to HSL is to the on hydrolytic HSL in the of the of the interaction of HSL with StAR and to the that the interaction of HSL with StAR might facilitate intracellular cholesterol trafficking to mitochondria for in adrenal cells, we adrenocortical cells with HSL as a triacylglycerol hydrolase. hydrolase is a neutral lipase that has been to possess triacylglycerol R. Biochem. J. 1999; PubMed Scopus Google Scholar) as well as cholesteryl ester S. PubMed Scopus Google Scholar) hydrolytic however, triacylglycerol hydrolase interact with StAR in in vitro pull-down experiments cells were with cholesteryl by with in the of for were in for to the of StAR to cells were treated with or for to StAR of cholesterol a specific of was in the were the mitochondria and mitochondrial cholesterol content by were low of StAR protein in cells, StAR cholesteryl ester with and for StAR to and with for StAR cholesterol content in cells with with and the of StAR, with the critical of StAR in cholesterol transfer of HSL in cells in the of mitochondrial cholesterol mitochondrial cholesterol content was by overexpression of HSL and with that observed in cells with and treated with In this in mitochondrial cholesterol content was cells were treated with and with triacylglycerol hydrolase. results suggest a of the interaction of HSL with StAR to facilitate cholesterol movement to of HSL with other proteins several in the (11Shen W.-J. Sridhar K. Bernlohr D.A. Kraemer F.B. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 5528-5532Crossref PubMed Scopus (182) Google Scholar, L.-J. Saltiel A.R. Mol. Cell. 1999; 4: 109-115Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar) have shown that HSL interacts specifically with intracellular proteins in adipose tissue. of a direct interaction of HSL with ALBP known as a of the of intracellular lipid-binding proteins that fatty acids, and other hydrophobic to the that HSL and ALBP a in adipose The physical interaction of ALBP with HSL has been shown to the hydrolytic activity of HSL and to HSL from product inhibition by fatty acids (13Shen W.-J. Liang Y. Hong R. Patel S. Natu V. Sridhar K. Jenkins A. Bernlohr D.A. Kraemer F.B. J. Biol. Chem. 2001; 276: 49443-49448Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar). In the current studies we have demonstrated a direct interaction of HSL with StAR, which has a of the of cholesteryl ester and the trafficking of intracellular cholesterol The interaction of HSL with StAR was first shown by in vitro pull-down experiments. of mutations of StAR, it that within the first acid and within the region amino acids and are to the interaction of StAR with HSL. The acid is in the of StAR and the that StAR to mitochondria and is the protein is processed in mitochondria to its mature 30-kDa (14Miller W.L. Strauss III, J.F. J. Steroid Biochem. Mol. Biol. 1999; 69: 131-141Crossref PubMed Scopus (145) Google Scholar, 15Stocco D.M. Annu. Rev. Physiol. 2001; 63: 193-213Crossref PubMed Scopus (695) Google Scholar). acids of StAR the and with the and are located of the a in the protein (20Tsujishita Y. Hurley J.H. Nat. Struct. Biol. 2000; 7: 408-414Crossref PubMed Scopus (446) Google Scholar). Based on the crystal structure of the StAR-related lipid transfer domain of the the and is located on the and available for with other proteins as HSL. In to interaction of HSL and StAR in the proteins were shown to interact in vivo in adrenal by the of StAR with HSL. that both the 37-kDa and the processed 30-kDa StAR with HSL. It is that the interaction of the 30-kDa StAR, which amino acids as a domain, within the adrenal because the 30-kDa StAR is within mitochondria D. 1999; PubMed Scopus Google Scholar), and HSL is within mitochondria (2Kraemer F.B. Shen W.-J. Natu V. Patel S. Osuga J.-i. Ishibashi S. Azhar S. Endocrinology. 2002; 143: 801-806Crossref PubMed Scopus (51) Google Scholar). the interaction of the 30-kDa StAR with HSL results from the of mitochondrial In the 37-kDa StAR is in cytosol with HSL and two amino acids and which can the of the of the interaction of StAR with HSL is in the of the cholesteryl ester hydrolytic activity of HSL. The for this in hydrolytic activity is the to experiments the interaction of ALBP with HSL. ALBP in HSL hydrolytic activity that is by the of ALBP to interact with HSL and the of ALBP to fatty acid (13Shen W.-J. Liang Y. Hong R. Patel S. Natu V. Sridhar K. Jenkins A. Bernlohr D.A. Kraemer F.B. J. Biol. Chem. 2001; 276: 49443-49448Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar). StAR possess fatty acid and the of fatty acids the of cholesteryl be to be to have the physical interaction of StAR with HSL might the of the enzyme to the catalytic or fatty acids from the enzyme through a or is a direct interaction in vitro and HSL hydrolytic of the which in and acid StAR proteins that can to HSL within the domain, hydrolytic activity, of of StAR and amino which can HSL through the region hydrolytic of a acid StAR that HSL the which amino acids hydrolytic amino acids to be for of HSL hydrolytic activity, other of StAR to be The step in to be the transfer of unesterified cholesterol from the outer mitochondrial to the inner where is located (14Miller W.L. Strauss III, J.F. J. Steroid Biochem. Mol. Biol. 1999; 69: 131-141Crossref PubMed Scopus (145) Google Scholar, 15Stocco D.M. Annu. Rev. Physiol. 2001; 63: 193-213Crossref PubMed Scopus (695) Google Scholar, Strauss III, J.F. 2000; PubMed Scopus Google Scholar). movement of cholesterol StAR and other proteins as the R.C. V. Rev. 2001; PubMed Google Scholar). to cholesterol be on the outer mitochondrial most the movement of cholesterol to the outer mitochondrial is because are a of of cholesterol. The the movement of cholesterol to the mitochondria have been well trafficking in cells is a that is and to a of movement and of the which of cholesterol in most cells, can and pathways C. P. J. Lipid Res. 1997; Full Text PDF PubMed Google Scholar, 1999; PubMed Scopus Google Scholar, D. Biol. 2000; PubMed Scopus Google Scholar). pathways to on lipid and The of cholesterol the of cholesteryl by acid lipase within and and the movement of the unesterified cholesterol of these as protein to be important in this the involved are 2000; PubMed Scopus Google Scholar). to be important in trafficking cholesterol for under conditions in which the for is by to be involved in trafficking other pathways for cholesterol for H. G. Patel S. Strauss III, J.F. Res. 2000; PubMed Scopus Google Scholar). a of the START domain has been to facilitate the movement of cholesterol to mitochondria for M. P. Fujimoto T. F. M. J.A. Strauss III, J.F. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). A and major of the interaction of StAR with HSL is suggested by experiments that the overexpression of HSL in the of StAR results in of the movement of cholesterol mitochondria in adrenal overexpression of a which no interaction with StAR in to cholesterol movement mitochondria that with StAR results the that StAR and HSL a in the adrenal to facilitate cholesterol movement to The physical of StAR with HSL within this unesterified cholesterol of cholesteryl to be and by synthesized StAR for first to the outer and to the of mitochondria for steroidogenesis. In this way the interaction of HSL with a StAR the step in the trafficking of intracellular cholesterol of the lipid in of the of of the START domain R.E. M.J. E. Burley S.K. Breslow J.L. Proc. Natl. Acad. Sci. U. S. A. 2002; 99: PubMed Scopus Google Scholar), some of which and are in tissues it is that the of interaction of HSL with StAR might the HSL might interact with or or experiments be to these