Metabolism of exogenous cholesterol by rat adrenal mitochondria is stimulated equally by physiological levels of free Ca2+ and by GTP

Molecular and Cellular Endocrinology
R KowluruC R Jefcoate

Abstract

Adrenal mitochondria metabolize cholesterol at inner membrane (IM) cytochrome P450scc. Exogenous and outer membrane (OM) cholesterol are metabolized more slowly due to a limiting transfer of cholesterol from OM to IM. This process is stimulated by in vivo ACTH treatment and inhibited by cycloheximide (CX)-induced depletion of labile regulatory proteins. In isolated rat adrenal mitochondria, GTP enhances the metabolism of exogenous cholesterol, consistent with enhanced intermembrane cholesterol transfer (Xu et al. (1989) J. Biol Chem. 264, 17674), but metabolism of 20 alpha-hydroxycholesterol, which readily traverses mitochondrial membranes, is not affected. The non-hydrolyzable analog, GTP gamma S, completely inhibits the activation of cholesterol metabolism by GTP, suggesting a requirement for GTP hydrolysis. Low concentrations of Ca2+ (0.4-4 microM) stimulate two independent cholesterol transport processes. For exogenous cholesterol, a Ca(2+)-mediated process can replace GTP since each produces comparable stimulation and the combination produces little additional activity. This Ca2+ stimulation is insensitive to GTP gamma S and also to Ruthenium Red (RR), which prevents Ca2+ entry into the matrix. Ca2+ also enhances availabil...Continue Reading

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Citations

Mar 18, 2004·Molecular and Cellular Endocrinology·András Spät, János G Pitter
Sep 21, 2000·Molecular and Cellular Endocrinology·S R KingD M Stocco
Apr 15, 2008·Trends in Endocrinology and Metabolism : TEM·N Cherradi, A M Capponi
May 15, 2002·The International Journal of Biochemistry & Cell Biology·Federico MartínezRebeca Milán
May 15, 2002·The International Journal of Biochemistry & Cell Biology·Federico MartínezOscar Flores-Herrera
Aug 16, 2016·Molecular and Cellular Endocrinology·Jinwoo LeeColin Jefcoate
Mar 27, 2004·Physiological Reviews·András Spät, László Hunyady
Jan 16, 2016·Molecular Endocrinology·Ye LinFredric B Kraemer
Oct 18, 1996·The Journal of Biological Chemistry·N CherradiA M Capponi
Sep 27, 2001·News in Physiological Sciences : an International Journal of Physiology Produced Jointly by the International Union of Physiological Sciences and the American Physiological Society·A SpätG Szabadkai
Apr 25, 2018·Journal of Molecular Endocrinology·Colin R Jefcoate, Jinwoo Lee
Jan 13, 2000·Biochimica Et Biophysica Acta·L S Sleer, P F Hall

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