ArticleEndocrinology2018
CRISPR/Cas9‒Mediated Tspo Gene Mutations Lead to Reduced Mitochondrial Membrane Potential and Steroid Formation in MA-10 Mouse Tumor Leydig Cells.
Article in Endocrinology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Single cell resolution of neurosteroidogenesis in the murine brain: de novo biosynthesis.The Journal of endocrinology · 2025Article
- The effects of bisphenol A and its analogs on steroidogenesis in MA-10 Leydig cells and KGN granulosa cells†.Biology of reproduction · 2025Article
- STK11 mutation affects tumor proliferation by impacting CD4Central-European journal of immunology · 2024Article
- Peripheral Ischemia Imprints Epigenetic Changes in Hematopoietic Stem Cells to Propagate Inflammation and Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Translocator protein in the rise and fall of central nervous system neurons.Frontiers in cellular neuroscience · 2023Review
- Basic Leucine Zipper Transcription Factors as Important Regulators of Leydig Cells' Functions.International journal of molecular sciences · 2022Review
- Cellular sources of TSPO expression in healthy and diseased brain.European journal of nuclear medicine and molecular imaging · 2021Review
- The AP-1 family of transcription factors are important regulators of gene expression within Leydig cells.Endocrine · 2021Review
- Absence of the mitochondrial translocator protein 18 kDa in mice does not affect body weight or food intake responses to altered energy availability.Journal of neuroendocrinology · 2021Article
- TSPO protein binding partners in bacteria, animals, and plants.Journal of bioenergetics and biomembranes · 2021Review
- Article
- TSPO ligand FGIN-1-27 controls priapism in sickle cell mice via endogenous testosterone production.Journal of cellular physiology · 2021Article
- De novo Neurosteroidogenesis in Human Microglia: Involvement of the 18 kDa Translocator Protein.International journal of molecular sciences · 2021Article
- Leydig Cell and Spermatogenesis.Advances in experimental medicine and biology · 2021Article
- Mitochondrial TSPO Deficiency Triggers Retrograde Signaling in MA-10 Mouse Tumor Leydig Cells.International journal of molecular sciences · 2020Article
- Review
- Effects of pharmacologically induced Leydig cell testosterone production on intratesticular testosterone and spermatogenesis†.Biology of reproduction · 2020Article
- Article
- Commentary:Frontiers in endocrinology · 2020Article
- Poly (ADP-ribose) polymerase inhibition protects against myocardial ischaemia/reperfusion injury via suppressing mitophagy.Journal of cellular and molecular medicine · 2019Article
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4 authors at 3 institutions in 2 countries.
Funding
Abstract
The outer mitochondrial membrane translocator protein (TSPO) binds cholesterol with high affinity and is involved in mediating its delivery into mitochondria, the rate-limiting step in hormone-induced steroidogenesis. Specific ligand binding to TSPO has been shown to initiate steroid formation. However, recent studies of the genetic deletion of Tspo have provided conflicting results. Here, we address and extend previous studies by examining the effects of Tspo-specific mutations on steroid formation in hormone- and cyclic adenosine monophosphate (cAMP)-responsive MA-10 cells, using the CRISPR/Cas9 system. Two mutant subcell lines, nG1 and G2G, each carrying a Tspo exon2-specific genome modification, and two control subcell lines, G1 and HH, each carrying a wild-type Tspo, were produced. In response to dibutyryl cAMP, the nG1 and G2G cells produced progesterone at levels significantly lower than those produced by the corresponding control cells G1 and HH. Neutral lipid homeostasis, which provides free cholesterol for steroid biosynthesis, was altered significantly in the Tspo mutant cells. Interestingly, the mitochondrial membrane potential (ΔΨm) of the Tspo mutant cells was significantly reduced compared with that of the control cells, likely because of TSPO interactions with the voltage-dependent anion channel and tubulin at the outer mitochondrial membrane. Steroidogenic acute regulatory protein (STAR) expression was induced in nG1 cells, suggesting that reduced TSPO affected STAR synthesis and/or processing. Taken together, these results provide further evidence for the critical role of TSPO in steroid biosynthesis and suggest that it may function at least in part via its regulation of ΔΨm and effects on STAR.
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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.