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An Outer Mitochondrial Translocase, Tom22, Is Crucial for Inner Mitochondrial Steroidogenic Regulation in Adrenal and Gonadal Tissues
- Source :
- Molecular and Cellular Biology. 36:1032-1047
- Publication Year :
- 2016
- Publisher :
- Informa UK Limited, 2016.
-
Abstract
- After cholesterol is transported into the mitochondria of steroidogenic tissues, the first steroid, pregnenolone, is synthesized in adrenal and gonadal tissues to initiate steroid synthesis by catalyzing the conversion of pregnenolone to progesterone, which is mediated by the inner mitochondrial enzyme 3β-hydroxysteroid dehydrogenase 2 (3βHSD2). We report that the mitochondrial translocase Tom22 is essential for metabolic conversion, as its knockdown by small interfering RNA (siRNA) completely ablated progesterone conversion in both steroidogenic mouse Leydig MA-10 and human adrenal NCI cells. Tom22 forms a 500-kDa complex with mitochondrial proteins associated with 3βHSD2. Although the absence of Tom22 did not inhibit mitochondrial import of cytochrome P450scc (cytochrome P450 side chain cleavage enzyme) 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 at the 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. Therefore, Tom22 is a critical regulator of steroidogenesis, and thus, it is essential for mammalian survival.
- Subjects :
- Male
0301 basic medicine
Aldosterone synthase
Molecular Sequence Data
Down-Regulation
030209 endocrinology & metabolism
Mitochondrion
Mitochondrial Membrane Transport Proteins
Mitochondrial apoptosis-induced channel
Cell Line
Mice
03 medical and health sciences
Mitochondrial membrane transport protein
0302 clinical medicine
Adrenal Glands
Mitochondrial Precursor Protein Import Complex Proteins
medicine
Animals
Humans
Translocase
Amino Acid Sequence
Protein Interaction Maps
RNA, Small Interfering
Molecular Biology
Cells, Cultured
Progesterone
biology
Progesterone Reductase
Cholesterol side-chain cleavage enzyme
Leydig Cells
Articles
Cell Biology
Mitochondria
Protein Transport
030104 developmental biology
Biochemistry
Mitochondrial Membranes
biology.protein
Pregnenolone
RNA Interference
ATP–ADP translocase
Sequence Alignment
medicine.drug
Subjects
Details
- ISSN :
- 10985549
- Volume :
- 36
- Database :
- OpenAIRE
- Journal :
- Molecular and Cellular Biology
- Accession number :
- edsair.doi.dedup.....41388fcaabfb2ff77bb81e1a1b9bece9