Outer mitochondrial translocase, Tom22, is crucial for inner mitochondrial steroidogenic regulation in adrenal and gonadal tissues

Molecular and Cellular Biology
Maheshinie RajapakshaHimangshu S Bose

Abstract

After cholesterol is transported into the mitochondria of steroidogenic tissues, the first steroid, pregnenolone, is synthesized in adrenals and gonadal tissues to initiate steroids synthesis by catalyzing pregnenolone to progesterone conversion, which is mediated by the inner mitochondrial enzyme, 3-beta hydroxysteroid dehydrogenase 2 (3βHSD2). We report that the mitochondrial translocase, Tom22, is essential for metabolic conversion as its knockdown by siRNA completely ablated progesterone conversion in both steroidogenic mouse Leydig MA-10 and human adrenal NCI cells. Tom22 forms a 500kDa complex with mitochondrial proteins associated with 3βHSD2. Although the absence of Tom22 did not inhibit mitochondrial import of P450scc and aldosterone synthase, it did inhibit 3βHSD2 expression. Electron microscopy showed that Tom22 is localized at the outer mitochondrial membrane (OMM) while 3βHSD2 is localized both at the OMM and inner mitochondrial space (IMS) where it interacts through a specific region with Tom22 with its C-terminal amino acids and a small amino acid segment of Tom22 exposed to the IMS. Thus, Tom22 is a critical regulator of steroidogenesis and thus it is essential for mammalian survival.

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Citations

Aug 4, 2016·Molecular and Cellular Endocrinology·Douglas M StoccoVimal Selvaraj
Aug 16, 2016·Molecular and Cellular Endocrinology·Jinwoo LeeColin Jefcoate
May 3, 2018·Biology of Reproduction·Vimal SelvarajBarbara J Clark
Jun 9, 2018·European Journal of Endocrinology·Walter L Miller
Oct 5, 2016·Molecular and Cellular Biology·Manoj PrasadHimangshu S Bose
Oct 24, 2018·Molecular and Cellular Biology·Himangshu S BoseRandy M Whittal
May 6, 2019·Endocrinology, Diabetes & Metabolism Case Reports·Himangshu S BoseElizabeth W Perry
Sep 20, 2019·International Journal of Molecular Sciences·Federico BaronioAntonio Balsamo
May 2, 2017·Endocrinology, Diabetes & Metabolism Case Reports·Anil PiyaHimangshu S Bose
Mar 10, 2017·Science Advances·Manoj PrasadHimangshu S Bose
Apr 25, 2018·Journal of Molecular Endocrinology·Colin R Jefcoate, Jinwoo Lee
Nov 18, 2016·Endocrinology, Diabetes & Metabolism Case Reports·Jasmeet KaurHimangshu S Bose
Dec 22, 2016·Frontiers in Neuroscience·Barbara J Clark
Feb 3, 2021·The Journal of Pharmacology and Experimental Therapeutics·Himangshu S BoseWalter L Miller

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