title: SNARE-Mediated Cholesterol Movement to Mitochondria Supports Steroidogenesis in Rodent Cells.
abstract: Vesicular transport involving soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) proteins is known to be responsible for many major cellular activities. In steroidogenic tissues, chronic hormone stimulation results in increased expression of proteins involved in the steroidogenic pathway, whereas acute hormone stimulation prompts the rapid transfer of cholesterol to the inner mitochondrial membrane to be utilized as substrate for steroid hormone production. Several different pathways are involved in supplying cholesterol to mitochondria, but mobilization of stored cholesteryl esters appears to initially constitute the preferred source; however, the mechanisms mediating this cholesterol transfer are not fully understood. To study the potential contribution of SNARE proteins in steroidogenesis, we examined the expression levels of various SNARE proteins in response to hormone stimulation in steroidogenic tissues and cells and established an in vitro mitochondria reconstitution assay system to assess the contribution of various SNARE proteins on cholesterol delivery for steroidogenesis. Our results from reconstitution experiments along with knockdown studies in rat primary granulosa cells and in a Leydig cell line show that soluble N-ethylmaleimide sensitive factor attachment protein-α, synaptosomal-associated protein of 25 kDa, syntaxin-5, and syntaxin-17 facilitate the transport of cholesterol to mitochondria. Thus, although StAR is required for efficient cholesterol movement into mitochondria for steroidogenesis, specific SNAREs participate and are necessary to mediate cholesterol movement to mitochondria.
authors.affiliation: Division of Endocrinology, Gerontology, and Metabolism (Y.L., X.H., W.-J.S., R.H., V.K.K., S.A., F.B.K.), Stanford University, and Veterans Affairs Palo Alto Health Care System (Y.L., X.H., W.-J.S., R.H., V.K.K., Y.C., A.N.R., S.A., F.B.K.), Palo Alto, California 94304.
authors.forename: Ye
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Division of Endocrinology, Gerontology, and Metabolism (Y.L., X.H., W.-J.S., R.H., V.K.K., S.A., F.B.K.), Stanford University, and Veterans Affairs Palo Alto Health Care System (Y.L., X.H., W.-J.S., R.H., V.K.K., Y.C., A.N.R., S.A., F.B.K.), Palo Alto, California 94304.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Hou
authors.affiliation: Division of Endocrinology, Gerontology, and Metabolism (Y.L., X.H., W.-J.S., R.H., V.K.K., S.A., F.B.K.), Stanford University, and Veterans Affairs Palo Alto Health Care System (Y.L., X.H., W.-J.S., R.H., V.K.K., Y.C., A.N.R., S.A., F.B.K.), Palo Alto, California 94304.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Shen
authors.affiliation: Division of Endocrinology, Gerontology, and Metabolism (Y.L., X.H., W.-J.S., R.H., V.K.K., S.A., F.B.K.), Stanford University, and Veterans Affairs Palo Alto Health Care System (Y.L., X.H., W.-J.S., R.H., V.K.K., Y.C., A.N.R., S.A., F.B.K.), Palo Alto, California 94304.
authors.forename: Ruth
authors.initials: R
authors.lastname: Hanssen
authors.affiliation: Division of Endocrinology, Gerontology, and Metabolism (Y.L., X.H., W.-J.S., R.H., V.K.K., S.A., F.B.K.), Stanford University, and Veterans Affairs Palo Alto Health Care System (Y.L., X.H., W.-J.S., R.H., V.K.K., Y.C., A.N.R., S.A., F.B.K.), Palo Alto, California 94304.
authors.forename: Victor K
authors.initials: VK
authors.lastname: Khor
authors.affiliation: Division of Endocrinology, Gerontology, and Metabolism (Y.L., X.H., W.-J.S., R.H., V.K.K., S.A., F.B.K.), Stanford University, and Veterans Affairs Palo Alto Health Care System (Y.L., X.H., W.-J.S., R.H., V.K.K., Y.C., A.N.R., S.A., F.B.K.), Palo Alto, California 94304.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cortez
authors.affiliation: Division of Endocrinology, Gerontology, and Metabolism (Y.L., X.H., W.-J.S., R.H., V.K.K., S.A., F.B.K.), Stanford University, and Veterans Affairs Palo Alto Health Care System (Y.L., X.H., W.-J.S., R.H., V.K.K., Y.C., A.N.R., S.A., F.B.K.), Palo Alto, California 94304.
authors.forename: Ann N
authors.initials: AN
authors.lastname: Roseman
authors.affiliation: Division of Endocrinology, Gerontology, and Metabolism (Y.L., X.H., W.-J.S., R.H., V.K.K., S.A., F.B.K.), Stanford University, and Veterans Affairs Palo Alto Health Care System (Y.L., X.H., W.-J.S., R.H., V.K.K., Y.C., A.N.R., S.A., F.B.K.), Palo Alto, California 94304.
authors.forename: Salman
authors.initials: S
authors.lastname: Azhar
authors.affiliation: Division of Endocrinology, Gerontology, and Metabolism (Y.L., X.H., W.-J.S., R.H., V.K.K., S.A., F.B.K.), Stanford University, and Veterans Affairs Palo Alto Health Care System (Y.L., X.H., W.-J.S., R.H., V.K.K., Y.C., A.N.R., S.A., F.B.K.), Palo Alto, California 94304.
authors.forename: Fredric B
authors.initials: FB
authors.lastname: Kraemer
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D013256:Steroids / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D011994:Recombinant Proteins; D050600:SNARE Proteins; D013256:Steroids; D002784:Cholesterol