Steroid hormone synthesis begins with the conversion of cholesterol into pregnenolone by the enzyme cytochrome P450scc in mitochondria. The cholesterol used to synthesize pregnenolone is derived mainly from endocytosed LDL cholesterol. How this LDL cholesterol is transported to mitochondria in the human placenta is not well understood. Recent work has focused on how STARD3/MLN64 controls cholesterol trafficking. The STARD3 protein has a START domain that associates with cholesterol. Why STARD3 is distributed mainly to late endosomes but not to mitochondria is an obstacle to understanding the early steps in steroidogenesis. STARD3 can bind the ER protein VAP and contribute to ER-late endosome MCS formation. In this review, recent progress on STARD3 functions suggests possible models to explain how cholesterol could transit to mitochondria via MCS.
| DOI | 10.11648/j.ajls.s.2015030302.19 |
| Published in |
American Journal of Life Sciences (Volume 3, Issue 3-2, May 2015)
This article belongs to the Special Issue Biology and Medicine of Peptide and Steroid Hormones |
| Page(s) | 48-52 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2024. Published by Science Publishing Group |
STARD3, steroidogenesis, endosome, mitochondria, cholesterol, membrane contact site
| [1] | E. Ikonen, "Cellular cholesterol trafficking and compartmentalization," Nat. Rev. Mol. Cell Biol., 2008, 9, pp. 125-138. |
| [2] | W.L. Miller, "Steroid hormone synthesis in mitochondria," Mol. Cell. Endocrinol., 2013, 379, pp. 62-73. |
| [3] | W.L. Miller, R.J. Auchus, "The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders," Endocr. Rev., 2011, 32, pp. 81-151. |
| [4] | J.F. Strauss, 3rd, C.B. Kallen, L.K. Christenson et al., "The steroidogenic acute regulatory protein (StAR): a window into the complexities of intracellular cholesterol trafficking," Recent Prog. Horm. Res., 1999, 54, pp. 369-394; discussion 394-365. |
| [5] | H.S. Bose, V.R. Lingappa, W.L. Miller, "Rapid regulation of steroidogenesis by mitochondrial protein import," Nature, 2002, 417, pp. 87-91. |
| [6] | B.J. Clark, J. Wells, S.R. King, D.M. Stocco, "The purification, cloning, and expression of a novel luteinizing hormone-induced mitochondrial protein in MA-10 mouse Leydig tumor cells. Characterization of the steroidogenic acute regulatory protein (StAR)," J. Biol. Chem., 1994, 269, pp. 28314-28322. |
| [7] | D. Lin, T. Sugawara, J.F. Strauss, 3rd et al., "Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis," Science, 1995, 267, pp. 1828-1831. |
| [8] | W.L. Miller, H.S. Bose, "Early steps in steroidogenesis: intracellular cholesterol trafficking," J. Lipid Res., 2011, 52, pp. 2111-2135. |
| [9] | T. Sugawara, J.A. Holt, D. Driscoll et al., "Human steroidogenic acute regulatory protein: functional activity in COS-1 cells, tissue-specific expression, and mapping of the structural gene to 8p11.2 and a pseudogene to chromosome 13," Proc. Natl. Acad. Sci. U. S. A., 1995, 92, pp. 4778-4782. |
| [10] | H.S. Bose, R.M. Whittal, M.C. Huang, M.A. Baldwin, W.L. Miller, "N-218 MLN64, a protein with StAR-like steroidogenic activity, is folded and cleaved similarly to StAR," Biochemistry, 2000, 39, pp. 11722-11731. |
| [11] | F. Alpy, M.E. Stoeckel, A. Dierich et al., "The steroidogenic acute regulatory protein homolog MLN64, a late endosomal cholesterol-binding protein," J. Biol. Chem., 2001, 276, pp. 4261-4269. |
| [12] | M. Zhang, P. Liu, N.K. Dwyer et al., "MLN64 mediates mobilization of lysosomal cholesterol to steroidogenic mitochondria," J. Biol. Chem., 2002, 277, pp. 33300-33310. |
| [13] | F. Alpy, A. Rousseau, Y. Schwab et al., "STARD3 or STARD3NL and VAP form a novel molecular tether between late endosomes and the ER," J. Cell Sci., 2013, 126, pp. 5500-5512. |
| [14] | R. van der Kant, I. Zondervan, L. Janssen, J. Neefjes, "Cholesterol-binding molecules MLN64 and ORP1L mark distinct late endosomes with transporters ABCA3 and NPC1," J. Lipid Res., 2013, 54, pp. 2153-2165. |
| [15] | M. Charman, B.E. Kennedy, N. Osborne, B. Karten, "MLN64 mediates egress of cholesterol from endosomes to mitochondria in the absence of functional Niemann-Pick Type C1 protein," J. Lipid Res., 2010, 51, pp. 1023-1034. |
| [16] | R.E. Soccio, J.L. Breslow, "StAR-related lipid transfer (START) proteins: mediators of intracellular lipid metabolism," J. Biol. Chem., 2003, 278, pp. 22183-22186. |
| [17] | F. Alpy, C. Tomasetto, "Give lipids a START: the StAR-related lipid transfer (START) domain in mammals," J. Cell Sci., 2005, 118, pp. 2791-2801. |
| [18] | G. D'Angelo, M. Vicinanza, M.A. De Matteis, "Lipid-transfer proteins in biosynthetic pathways," Curr. Opin. Cell Biol., 2008, 20, pp. 360-370. |
| [19] | B. Mesmin, B. Antonny, G. Drin, "Insights into the mechanisms of sterol transport between organelles," Cell. Mol. Life Sci., 2013, 70, pp. 3405-3421. |
| [20] | M. Murcia, J.D. Faraldo-Gomez, F.R. Maxfield, B. Roux, "Modeling the structure of the StART domains of MLN64 and StAR proteins in complex with cholesterol," J. Lipid Res., 2006, 47, pp. 2614-2630. |
| [21] | R.C. Tuckey, H.S. Bose, I. Czerwionka, W.L. Miller, "Molten globule structure and steroidogenic activity of N-218 MLN64 in human placental mitochondria," Endocrinology, 2004, 145, pp. 1700-1707. |
| [22] | H. Watari, F. Arakane, C. Moog-Lutz et al., "MLN64 contains a domain with homology to the steroidogenic acute regulatory protein (StAR) that stimulates steroidogenesis," Proc. Natl. Acad. Sci. U. S. A., 1997, 94, pp. 8462-8467. |
| [23] | J. Reitz, K. Gehrig-Burger, J.F. Strauss, 3rd, G. Gimpl, "Cholesterol interaction with the related steroidogenic acute regulatory lipid-transfer (START) domains of StAR (STARD1) and MLN64 (STARD3)," Febs j, 2008, 275, pp. 1790-1802. |
| [24] | M. Esparza-Perusquia, S. Olvera-Sanchez, O. Flores-Herrera et al., "Mitochondrial proteases act on STARD3 to activate progesterone synthesis in human syncytiotrophoblast," Biochim. Biophys. Acta, 2015, 1850, pp. 107-117. |
| [25] | F. Alpy, C. Tomasetto, "MLN64 and MENTHO, two mediators of endosomal cholesterol transport," Biochem. Soc. Trans., 2006, 34, pp. 343-345. |
| [26] | F. Alpy, V.K. Latchumanan, V. Kedinger et al., "Functional characterization of the MENTAL domain," J. Biol. Chem., 2005, 280, pp. 17945-17952. |
| [27] | G. Tzivion, J. Avruch, "14-3-3 proteins: active cofactors in cellular regulation by serine/threonine phosphorylation," J. Biol. Chem., 2002, 277, pp. 3061-3064. |
| [28] | A. Liapis, F.W. Chen, J.P. Davies, R. Wang, Y.A. Ioannou, "MLN64 transport to the late endosome is regulated by binding to 14-3-3 via a non-canonical binding site," PLoS One, 2012, 7, pp. e34424. |
| [29] | M. Holtta-Vuori, F. Alpy, K. Tanhuanpaa et al., "MLN64 is involved in actin-mediated dynamics of late endocytic organelles," Mol. Biol. Cell, 2005, 16, pp. 3873-3886. |
| [30] | W. Mobius, E. van Donselaar, Y. Ohno-Iwashita et al., "Recycling compartments and the internal vesicles of multivesicular bodies harbor most of the cholesterol found in the endocytic pathway," Traffic, 2003, 4, pp. 222-231. |
| [31] | T. Levine, C. Loewen, "Inter-organelle membrane contact sites: through a glass, darkly," Curr. Opin. Cell Biol., 2006, 18, pp. 371-378. |
| [32] | M. Lebiedzinska, G. Szabadkai, A.W. Jones, J. Duszynski, M.R. Wieckowski, "Interactions between the endoplasmic reticulum, mitochondria, plasma membrane and other subcellular organelles," Int. J. Biochem. Cell Biol., 2009, 41, pp. 1805-1816. |
| [33] | Y. Elbaz, M. Schuldiner, "Staying in touch: the molecular era of organelle contact sites," Trends Biochem. Sci., 2011, 36, pp. 616-623. |
| [34] | A. Toulmay, W.A. Prinz, "Lipid transfer and signaling at organelle contact sites: the tip of the iceberg," Curr. Opin. Cell Biol., 2011, 23, pp. 458-463. |
| [35] | T. Hayashi, R. Rizzuto, G. Hajnoczky, T.P. Su, "MAM: more than just a housekeeper," Trends Cell Biol., 2009, 19, pp. 81-88. |
| [36] | Y. Lange, J. Ye, M. Rigney, T.L. Steck, "Regulation of endoplasmic reticulum cholesterol by plasma membrane cholesterol," J. Lipid Res., 1999, 40, pp. 2264-2270. |
| [37] | D.L. Brasaemle, A.D. Attie, "Rapid intracellular transport of LDL-derived cholesterol to the plasma membrane in cultured fibroblasts," J. Lipid Res., 1990, 31, pp. 103-112. |
APA Style
Atsuki Nara, Tohru Komiya. (2015). STARD3/MLN64 is Striving at Membrane Contact Sites: Intracellular Cholesterol Trafficking for Steroidogenesis in Human Placental Cells. American Journal of Life Sciences, 3(3-2), 48-52. https://doi.org/10.11648/j.ajls.s.2015030302.19
ACS Style
Atsuki Nara; Tohru Komiya. STARD3/MLN64 is Striving at Membrane Contact Sites: Intracellular Cholesterol Trafficking for Steroidogenesis in Human Placental Cells. Am. J. Life Sci. 2015, 3(3-2), 48-52. doi: 10.11648/j.ajls.s.2015030302.19
AMA Style
Atsuki Nara, Tohru Komiya. STARD3/MLN64 is Striving at Membrane Contact Sites: Intracellular Cholesterol Trafficking for Steroidogenesis in Human Placental Cells. Am J Life Sci. 2015;3(3-2):48-52. doi: 10.11648/j.ajls.s.2015030302.19
Share This Article
Twitter
Linked In
Facebook
Copy
Download@article{10.11648/j.ajls.s.2015030302.19,
author = {Atsuki Nara and Tohru Komiya},
title = {STARD3/MLN64 is Striving at Membrane Contact Sites: Intracellular Cholesterol Trafficking for Steroidogenesis in Human Placental Cells},
journal = {American Journal of Life Sciences},
volume = {3},
number = {3-2},
pages = {48-52},
doi = {10.11648/j.ajls.s.2015030302.19},
url = {https://doi.org/10.11648/j.ajls.s.2015030302.19},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajls.s.2015030302.19},
abstract = {Steroid hormone synthesis begins with the conversion of cholesterol into pregnenolone by the enzyme cytochrome P450scc in mitochondria. The cholesterol used to synthesize pregnenolone is derived mainly from endocytosed LDL cholesterol. How this LDL cholesterol is transported to mitochondria in the human placenta is not well understood. Recent work has focused on how STARD3/MLN64 controls cholesterol trafficking. The STARD3 protein has a START domain that associates with cholesterol. Why STARD3 is distributed mainly to late endosomes but not to mitochondria is an obstacle to understanding the early steps in steroidogenesis. STARD3 can bind the ER protein VAP and contribute to ER-late endosome MCS formation. In this review, recent progress on STARD3 functions suggests possible models to explain how cholesterol could transit to mitochondria via MCS.},
year = {2015}
}
TY - JOUR T1 - STARD3/MLN64 is Striving at Membrane Contact Sites: Intracellular Cholesterol Trafficking for Steroidogenesis in Human Placental Cells AU - Atsuki Nara AU - Tohru Komiya Y1 - 2015/05/06 PY - 2015 N1 - https://doi.org/10.11648/j.ajls.s.2015030302.19 DO - 10.11648/j.ajls.s.2015030302.19 T2 - American Journal of Life Sciences JF - American Journal of Life Sciences JO - American Journal of Life Sciences SP - 48 EP - 52 PB - Science Publishing Group SN - 2328-5737 UR - https://doi.org/10.11648/j.ajls.s.2015030302.19 AB - Steroid hormone synthesis begins with the conversion of cholesterol into pregnenolone by the enzyme cytochrome P450scc in mitochondria. The cholesterol used to synthesize pregnenolone is derived mainly from endocytosed LDL cholesterol. How this LDL cholesterol is transported to mitochondria in the human placenta is not well understood. Recent work has focused on how STARD3/MLN64 controls cholesterol trafficking. The STARD3 protein has a START domain that associates with cholesterol. Why STARD3 is distributed mainly to late endosomes but not to mitochondria is an obstacle to understanding the early steps in steroidogenesis. STARD3 can bind the ER protein VAP and contribute to ER-late endosome MCS formation. In this review, recent progress on STARD3 functions suggests possible models to explain how cholesterol could transit to mitochondria via MCS. VL - 3 IS - 3-2 ER -
Information
Email: