ArticleProceedings of the National Academy of Sciences of the United States of America1996
Steroidogenic acute regulatory protein (StAR) retains activity in the absence of its mitochondrial import sequence: implications for the mechanism of StAR action.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 306 citations in OpenAlex.
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- Adrenal rather than central dysfunction limits hypothalamic-pituitary-adrenal axis recovery after chronic glucocorticoid treatment in male mice.Endocrinology · 2026Article
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- Adrenocortical Mitochondria-Associated Membranes: Isolation, Characterization, and Lipidoproteomic Response to Mitotane.Journal of the Endocrine Society · 2026Article
- Mitochondrial depolarization stabilizes the vitamin B12 chaperone MMADHC in the cytosol to increase MTR activity.bioRxiv : the preprint server for biology · 2025Article
- Discovery and development of steroidal enzyme inhibitors as anti-cancer drugs: state-of-the-art and future perspectives.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- STAR/STARD1: A mitochondrial intermembrane space cholesterol shuttle degraded through mitophagy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Steroidogenic Acute Regulatory (STAR) Gene Anatomy, Expression, and Roles.Development & reproduction · 2025Review
- Using of transporter proteins to improve the uptake efficiency of hydrophobic compounds by Escherichia coli: a coordinated synthesis of START protein and P450scc system proteins to enhance cholesterol biotransformation.Bioresources and bioprocessing · 2025Article
- LRP1 immunotherapy enhances cardiomyocyte respiration by restricting cholesteryl ester accumulation in mitochondria.Journal of lipid research · 2025Article
- Thirty years of StAR gazing. Expanding the universe of the steroidogenic acute regulatory protein.The Journal of endocrinology · 2025Review
- Increased Steroidogenic Acute Regulatory Protein Contributes to Cholesterol-induced β-Cell Dysfunction.Endocrinology · 2025Article
- The conformational plasticity of structurally unrelated lipid transport proteins correlates with their mode of action.PLoS biology · 2024Article
- Local Effects of Steroid Hormones within the Bone Microenvironment.International journal of molecular sciences · 2023Review
- New molecular insights into the A218V variant impact on the steroidogenic acute regulatory protein (STAR) associated with 46, XY disorders of sexual development.Molecular genetics and genomics : MGG · 2023Article
- Tom40 in cholesterol transport.iScience · 2023Article
- Clinical and functional analyses of the novel STAR c.558C>A in a patient with classic lipoid congenital adrenal hyperplasia.Frontiers in genetics · 2023Article
- Role of STAR and SCP2/SCPx in the Transport of Cholesterol and Other Lipids.International journal of molecular sciences · 2022Review
- Mechanism of Action of an Environmentally Relevant Organochlorine Mixture in Repressing Steroid Hormone Biosynthesis in Leydig Cells.International journal of molecular sciences · 2022Article
- Review
19 more citing papers are in PubMed but not listed here.
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9 authors at 3 institutions in 1 country.
Funding
Abstract
Steroidogenic acute regulatory protein (StAR) plays a critical role in steroid hormone biosynthesis, presumably by facilitating the delivery of cholesterol to P450scc in the inner mitochondrial membranes. StAR is synthesized as a 37-kDa preprotein that is processed to a 30-kDa mature form by cleavage of an N-terminal mitochondrial import sequence. To identify structural features required for StAR biological activity, we mutated the human StAR cDNA, including the deletion of N- and C-terminal sequences, and examined the ability of the mutants to promote steroidogenesis and enter the mitochondria of transfected COS-1 cells. Deletion of up to 62 residues from the N terminus (N-62) did not significantly affect steroidogenesis-enhancing activity. The N-terminal deletion mutants were associated with mitochondria-enriched fractions, but import and processing were progressively impaired with increasing length of the deletion. Immunogold electron microscopy and in vitro import assays showed that the active N-62 mutant was not imported into the mitochondria. Removal of the 28 C-terminal amino acids (C-28) inactivated StAR. Deletion of the C-terminal 10 amino acids (C-10) reduced steroidogenic activity by 53%, while truncation of the last 4 amino acids had no effect. The C-28 mutant StAR was not efficiently imported into mitochondria or processed, whereas some of the C-10 mutant was processed, indicating that import had occurred. We conclude that in the COS-1 cell system used, StAR does not need to enter into mitochondria to stimulate steroidogenesis and that residues in the C terminus are essential for steroidogenesis-enhancing activity. These findings imply that StAR acts via C-terminal domains on the outside of the mitochondria.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.