ArticleThe Journal of biological chemistry2015
Deficiency in the Lipid Exporter ABCA1 Impairs Retrograde Sterol Movement and Disrupts Sterol Sensing at the Endoplasmic Reticulum.
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 40 papers.
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Who cites it
40 citing papers in PubMed, 63 citations in OpenAlex.
- Balancing cholesterol metabolism in the liver and gut: perspectives in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- The Contribution of Cholesterol and Squalene Synthase in Cancer: Molecular Mechanisms, Lipid Rafts and Therapeutic Approaches.Medicinal research reviews · 2026Review
- Ferredoxin 2 Is Critical for Tumor Suppression and Lipid Homeostasis but Dispensable for Embryonic Development.The American journal of pathology · 2025Article
- A novel role for Friend of GATA1 (FOG-1) in regulating cholesterol transport in murine erythropoiesis.PLoS genetics · 2025Article
- Article
- Towards a Unitary Hypothesis of Alzheimer's Disease Pathogenesis.Journal of Alzheimer's disease : JAD · 2024Article
- Is reverse cholesterol transport regulated by active cholesterol?Journal of lipid research · 2023Review
- PI(4,5)PAdvances in experimental medicine and biology · 2023Article
- Microglia and Cholesterol Handling: Implications for Alzheimer's Disease.Biomedicines · 2022Review
- Implantable Electroceutical Approach Improves Myelination by Restoring Membrane Integrity in a Mouse Model of Peripheral Demyelinating Neuropathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Article
- Ferredoxin reductase and p53 are necessary for lipid homeostasis and tumor suppression through the ABCA1-SREBP pathway.Oncogene · 2022Article
- Cholesterol-Lowering Phytochemicals: Targeting the Mevalonate Pathway for Anticancer Interventions.Frontiers in genetics · 2022Review
- Blocking cholesterol storage to treat Alzheimer's disease.Exploration of neuroprotective therapy · 2021Article
- Current Diagnosis and Management of Tangier Disease.Journal of atherosclerosis and thrombosis · 2021Review
- Salmonella Typhimurium manipulates macrophage cholesterol homeostasis through the SseJ-mediated suppression of the host cholesterol transport protein ABCA1.Cellular microbiology · 2021Article
- Targeting the Mevalonate Pathway in Cancer.Trends in cancer · 2021Review
- Molecular Mechanisms Underpinning the Circulation and Cellular Uptake ofFrontiers in pharmacology · 2021Article
- Role of Cholesterol and Lipid Rafts in Cancer Signaling: A Promising Therapeutic Opportunity?Frontiers in cell and developmental biology · 2021Review
- The p53 Family: A Role in Lipid and Iron Metabolism.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Cellular cholesterol homeostasis involves sterol sensing at the endoplasmic reticulum (ER) and sterol export from the plasma membrane (PM). Sterol sensing at the ER requires efficient sterol delivery from the PM; however, the macromolecules that facilitate retrograde sterol transport at the PM have not been identified. ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol and phospholipid export to apolipoprotein A-I for the assembly of high density lipoprotein (HDL). Mutations in ABCA1 cause Tangier disease, a familial HDL deficiency. Several lines of clinical and experimental evidence suggest a second function of ABCA1 in cellular cholesterol homeostasis in addition to mediating cholesterol efflux. Here, we report the unexpected finding that ABCA1 also plays a key role in facilitating retrograde sterol transport from the PM to the ER for sterol sensing. Deficiency in ABCA1 delays sterol esterification at the ER and activates the SREBP-2 cleavage pathway. The intrinsic ATPase activity in ABCA1 is required to facilitate retrograde sterol transport. ABCA1 deficiency causes alternation of PM composition and hampers a clathrin-independent endocytic activity that is required for ER sterol sensing. Our finding identifies ABCA1 as a key macromolecule facilitating bidirectional sterol movement at the PM and shows that ABCA1 controls retrograde sterol transport by modulating a certain clathrin-independent endocytic process.
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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.