ArticleThe Journal of biological chemistry2015
Mitochondria-associated endoplasmic reticulum membrane (MAM) regulates steroidogenic activity via steroidogenic acute regulatory protein (StAR)-voltage-dependent anion channel 2 (VDAC2) interaction.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 156 citations in OpenAlex.
- The Interplay of Microtubules with Mitochondria-ER Contact Sites (MERCs) in Glioblastoma.Biomolecules · 2022Pooled it
- Research progress on VDAC2 in mitochondrial dysfunction-related diseases.Molecular biology reports · 2026Review
- Crosstalk collapse: mitochondria-centric organelle network disruption in ovarian aging.Cell communication and signaling : CCS · 2026Review
- Mechanisms of mitochondrial dysfunction in premature ovarian insufficiency.Journal of ovarian research · 2026Review
- Targeting Neuroinflammation in Depression: The Integrative Role of Sigma-1 Receptor Modulation.Journal of neurochemistry · 2026Review
- Mitochondrial interplay with membrane organelles in health and disease.Cell communication and signaling : CCS · 2026Review
- Mitochondria-ER crosstalk via MAMS: Bridging cellular homeostasis and cancer progression.Apoptosis : an international journal on programmed cell death · 2026Review
- Excitotoxicity in amyotrophic lateral sclerosis: a key pathogenic mechanism.Brain communications · 2026Review
- The role of mitochondria-endoplasmic reticulum crosstalk in colorectal cancer.Genes & diseases · 2026Review
- The role of mitochondrial-associated endoplasmic reticulum membranes (MAMs) in diabetic microvascular complications: a review.Cell death & disease · 2025Review
- Neuromedin B drives goat granulosa cell proliferation via NMBR-mediated calcium homeostasis.Journal of ovarian research · 2025Article
- Inhibition of NPC Intracellular Cholesterol Transporter 1 Dually Regulates Aldosterone Secretion Via the Steroidogenic Acute Regulatory-Related Lipid Transfer Domain-3-Voltage-Dependent Anion Channel 1 Axis and Inositol 1,4,5-Trisphosphate Receptor Type 3-Calcium Signaling.Journal of the American Heart Association · 2025Article
- From cholesterol to glucose: uncovering how statins induce β-cell dysfunction to promote type 2 diabetes.The Journal of endocrinology · 2025Review
- Thirty years of StAR gazing. Expanding the universe of the steroidogenic acute regulatory protein.The Journal of endocrinology · 2025Review
- Remodeling of Mitochondria-Endoplasmic Reticulum Contact Sites Accompanies LUHMES Differentiation.Biomolecules · 2025Article
- Lipid metabolism in the adrenal gland.Frontiers in endocrinology · 2025Review
- Mitochondria associated membranes in dilated cardiomyopathy: connecting pathogenesis and cellular dysfunction.Frontiers in cardiovascular medicine · 2025Review
- MiR-4769-3p suppresses adipogenesis in systemic sclerosis by negatively regulating the USP18/VDAC2 pathway.iScience · 2024Article
- Dry molten globule conformational state of CYP11A1 (SCC) regulates the first step of steroidogenesis in the mitochondrial matrix.iScience · 2024Article
- A-Syn(ful) MAM: A Fresh Perspective on a Converging Domain in Parkinson's Disease.International journal of molecular sciences · 2024Review
31 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Steroid hormones are essential for carbohydrate metabolism, stress management, and reproduction and are synthesized from cholesterol in mitochondria of adrenal glands and gonads/ovaries. In acute stress or hormonal stimulation, steroidogenic acute regulatory protein (StAR) transports substrate cholesterol into the mitochondria for steroidogenesis by an unknown mechanism. Here, we report for the first time that StAR interacts with voltage-dependent anion channel 2 (VDAC2) at the mitochondria-associated endoplasmic reticulum membrane (MAM) prior to its translocation to the mitochondrial matrix. In the MAM, StAR interacts with mitochondrial proteins Tom22 and VDAC2. However, Tom22 knockdown by siRNA had no effect on pregnenolone synthesis. In the absence of VDAC2, StAR was expressed but not processed into the mitochondria as a mature 30-kDa protein. VDAC2 interacted with StAR via its C-terminal 20 amino acids and N-terminal amino acids 221-229, regulating the mitochondrial processing of StAR into the mature protein. In the absence of VDAC2, StAR could not enter the mitochondria or interact with MAM-associated proteins, and therefore steroidogenesis was inhibited. Furthermore, the N terminus was not essential for StAR activity, and the N-terminal deletion mutant continued to interact with VDAC2. The endoplasmic reticulum-targeting prolactin signal sequence did not affect StAR association with the MAM and thus its mitochondrial targeting. Therefore, VDAC2 controls StAR processing and activity, and MAM is thus a central location for initiating mitochondrial steroidogenesis.
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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.