ArticleMolecular metabolism2020
Aster-B coordinates with Arf1 to regulate mitochondrial cholesterol transport.
Article in Molecular metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
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- The multimodal transcriptional response of denervated skeletal muscle involves regulation ofProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Aster-B Modulates Oxidative Stress Responses and Carotenoid Distribution in ARPE-19 Cells.Antioxidants (Basel, Switzerland) · 2025Article
- Unveiling BCO2 function in macular pigment metabolism: Mitochondrial processing and expression in the primate retina.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Article
- Distinct pathways for the absorption and metabolism of β-carotene and zeaxanthin in the mouse intestine.Journal of lipid research · 2025Article
- Lipid metabolism in the adrenal gland.Frontiers in endocrinology · 2025Review
- Genetic overlap between Alzheimer's disease and immune-mediated diseases: an atlas of shared genetic determinants and biological convergence.Molecular psychiatry · 2024Article
- Endogenous and fluorescent sterols reveal the molecular basis for ligand selectivity of human sterol transporters.bioRxiv : the preprint server for biology · 2024Article
- Effects of carotenoids on mitochondrial dysfunction.Biochemical Society transactions · 2024Review
- MicroRNA regulation of adrenal glucocorticoid and androgen biosynthesis.Vitamins and hormones · 2024Article
- Towards a Unitary Hypothesis of Alzheimer's Disease Pathogenesis.Journal of Alzheimer's disease : JAD · 2024Article
- Article
- Genetic overlap between Alzheimer's disease and immune-mediated diseases: An atlas of shared genetic determinants and biological convergence.Research square · 2023Article
- Intracellular Cholesterol Trafficking.Cold Spring Harbor perspectives in biology · 2023Review
- Identifying the Transcriptional Drivers of Metastasis Embedded within Localized Melanoma.Cancer discovery · 2023Article
- Pooled analysis of frontal lobe transcriptomic data identifies key mitophagy gene changes in Alzheimer's disease brain.Frontiers in aging neuroscience · 2023Article
- Aster la vista: Unraveling the biochemical basis of carotenoid homeostasis in the human retina.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Article
- The cholesterol transport protein GRAMD1C regulates autophagy initiation and mitochondrial bioenergetics.Nature communications · 2022Article
- De novo labeling and trafficking of individual lipid species in live cells.Molecular metabolism · 2022Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveCholesterol plays a pivotal role in mitochondrial steroidogenesis, membrane structure, and respiration. Mitochondrial membranes are intrinsically low in cholesterol content and therefore must be replenished with cholesterol from other subcellular membranes. However, the molecular mechanisms underlying mitochondrial cholesterol transport remains poorly understood. The Aster-B gene encodes a cholesterol binding protein recently implicated in cholesterol trafficking from the plasma membrane to the endoplasmic reticulum (ER). In this study, we investigated the function and underlying mechanism of Aster-B in mediating mitochondrial cholesterol transport.
methodsCRISPR/Cas9 gene editing was carried out to generate cell lines deficient in Aster-B expression. The effect of Aster-B deficiency on mitochondrial cholesterol transport was examined by both confocal imaging analysis and biochemical assays. Deletion mutational analysis was also carried out to identify the function of a putative mitochondrial targeting sequence (MTS) at the N-terminus of Aster-B for its role in targeting Aster-B to mitochondria and in mediating mitochondrial cholesterol trafficking.
resultsAblation of Aster-B impaired cholesterol transport from the ER to mitochondria, leading to a significant decrease in mitochondrial cholesterol content. Aster-B is also required for mitochondrial transport of fatty acids derived from hydrolysis of cholesterol esters. A putative MTS at the N-terminus of Aster-B mediates the mitochondrial cholesterol uptake. Deletion of the MTS or ablation of Arf1 GTPase which is required for mitochondrial translocation of ER proteins prevented mitochondrial cholesterol transport, leading to mitochondrial dysfunction.
conclusionsWe identified Aster-B as a key regulator of cholesterol transport from the ER to mitochondria. Aster-B also coordinates mitochondrial cholesterol trafficking with uptake of fatty acids derived from cholesterol esters, implicating the Aster-B protein as a novel regulator of steroidogenesis.
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