Peripheral-type benzodiazepine receptor-mediated action of steroidogenic acute regulatory protein on cholesterol entry into Leydig cell mitochondria
Open accessAbstract
Hormone-induced steroid biosynthesis begins with the transfer of cholesterol from intracellular stores into mitochondria. Steroidogenic acute regulatory protein (StAR) and peripheral-type benzodiazepine receptor (PBR) have been implicated in this rate-determining step of steroidogenesis. MA-10 mouse Leydig tumor cells were treated with and without oligodeoxynucleotides (ODNs) antisense to PBR and StAR followed by treatment with saturating concentrations of human choriogonadotropin. Treatment with ODNs antisense but not missense for both proteins inhibited the respective protein expression and the ability of the cells to synthesize steroids in response to human choriogonadotropin. Treatment of the cells with either ODNs antisense to PBR or a transducible peptide antagonist to PBR resulted in inhibition of the accumulation of the mature mitochondrial 30-kDa StAR protein, suggesting that the presence of PBR is required for StAR import into mitochondria. Addition of in vitro transcribed/translated 37-kDa StAR or a fusion protein of Tom20 (translocase of outer membrane) and StAR (Tom/StAR) to mitochondria isolated from control cells increased pregnenolone formation. Mitochondria isolated from cells treated with ODNs antisense, but not missense, to PBR failed to form pregnenolone and respond to either StAR or Tom/StAR proteins. Reincorporation of in vitro transcribed/translated PBR, but not PBR missing the cholesterol-binding domain, into MA-10 mitochondria rescued the ability of the mitochondria to form steroids and the ability of the mitochondria to respond to StAR and Tom/StAR proteins. These data suggest that both StAR and PBR proteins are indispensable elements of the steroidogenic machinery and function in a coordinated manner to transfer cholesterol into mitochondria.
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StAR appears to interact with peripheral benzodiazepine receptor, voltage-dependent anion channel 1, and phosphate carrier protein, all proteins found on the OMM.
“StAR appears to interact with peripheral benzodiazepine receptor (84), voltage-dependent anion channel 1, and phosphate carrier protein (86), all proteins found on the OMM.”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [84]
Substantial data indicate that the action of StAR also requires the translocator protein, TSPO, on the OMM.
“Substantial data indicate that the action of StAR also requires the translocator protein, TSPO (also known as the peripheral benzodiazepine receptor) on the OMM (83-85).”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [84]
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Self-citation
- Authors
- Hauet, T., Yao, Z.-X., Bose, H. S., Wall, C. T., Han, Z., Li, W., Hales, D. B., Miller, W. L., Culty, M., & Papadopoulos, V.
- Affiliations
- Georgetown University Medical Center (US)
- Department of Biochemistry and Molecular Biology (T.H., Z.-X.Y., C.T.W., Z.H., W.L., M.C., V.P.) Georgetown University Medical Center, Washington, DC 20057;
- University of California, San Francisco (US)
- University of Illinois Chicago (US)
- Corresponding author
- Papadopoulos, Vassilios
- ORCID
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2005-02-01
- Volume
- 19
- Issue
- 2
- Pages
- 540-554
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- OpenAlex
- W1966541444
- Semantic Scholar
- ef7e3760661b92876753b5b3c2d4dc2ca286da88
- Cited by
- 252
- References
- 49
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 8 · 2023: 6 · 2022: 8 · 2021: 7 · 2020: 6 · 2019: 7 · 2018: 5 · 2017: 6 · 2016: 14 · 2015: 17 · 2014: 18 · 2013: 18 · 2012: 16
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Georgetown University
- National Institutes of Health (1r01hd037032-01)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-37922, R01DK037922)
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 37032)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- steroidogenic acute regulatory protein, translocator protein (TSPO), cholesterol transport, Leydig cells, mitochondrial protein import, steroidogenesis, pregnenolone synthesis, antisense oligodeoxynucleotides, choriogonadotropin, MA-10 cells
- MeSH terms
- Steroidogenic Acute Regulatory Protein, Animals, Cell Survival, Cholesterol, Dose-Response Relationship, Drug, Gonadotropins, Humans, Hydroxycholesterols, Kinetics, Leydig Cells, Ligands, Male, Mitochondria, Mutation, Oligonucleotides, Peptides, Phosphoproteins, Pregnenolone, Protein Binding, Receptors, GABA-A, Steroids, Time Factors, Transcription, Genetic, Transfection, Protein Biosynthesis, Immunoblotting, Blotting, Western, Oligonucleotides, Antisense, Cyclic AMP-Dependent Protein Kinases, Mutation, Missense, RNA, Small Interfering, Cell Line, Tumor, Mice, In Vitro Techniques
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