ArticleMolecular and cellular biology2019
Inner Mitochondrial Translocase Tim50 Is Central in Adrenal and Testicular Steroid Synthesis.
Article in Molecular and cellular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- 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
- Thirty years of StAR gazing. Expanding the universe of the steroidogenic acute regulatory protein.The Journal of endocrinology · 2025Review
- Biochemical and neurophysiological effects of deficiency of the mitochondrial import protein TIMM50.eLife · 2024Article
- Dry molten globule conformational state of CYP11A1 (SCC) regulates the first step of steroidogenesis in the mitochondrial matrix.iScience · 2024Article
- Tom40 in cholesterol transport.iScience · 2023Article
- Diverse Functions of Tim50, a Component of the Mitochondrial Inner Membrane Protein Translocase.International journal of molecular sciences · 2021Review
- Skeletal Phenotypes Due to Abnormalities in Mitochondrial Protein Homeostasis and Import.International journal of molecular sciences · 2020Review
- Article
- Deficient pregnenolone synthesis associated with congenital adrenal hyperplasia and organelle dysfunction.Endocrinology, diabetes & metabolism case reports · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Adrenal and gonadal mitochondrial metabolic activity requires electrons from cofactors, cholesterol, and a substrate for rapid steroid synthesis, an essential requirement for mammalian survival. Substrate activity depends on its environment, which is regulated by chaperones and mitochondrial translocases. Cytochrome P450 side-chain cleavage enzyme (SCC or CYP11A1) catalyzes cholesterol to pregnenolone conversion, although its mechanism of action is not well understood. We find that SCC is directly imported into the mitochondrial matrix, where its N-terminal sequence is cleaved sequentially, after which it becomes activated following the second cleavage, which is dependent on the folding of the protein. Following integration of the SCC C terminus into the TIM23 complex, amino acids 141 to 146 interact with the intermembrane-exposed Tim50 protein, forming a large complex. The absence of Tim50 or its mutation reduced enzymatic activity. For the first time, we report that a protein activated at the matrix remains mostly unfolded and is transported back to the IMS to integrate with the TIM23 translocase complex and align with the Tim50 protein. Amino acid changes that suppress the association of Tim50 with SCC ablate metabolic activity. Thus, the TIM23 complex is the central regulator of metabolism guided by Tim50.
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Registered trials
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.