ArticleBiochemistry2016
An Unrecognized Function of Cholesterol: Regulating the Mechanism Controlling Membrane Phospholipid Asymmetry.
Article in Biochemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- Eryptosis and oxidative damage in hypertensive and dyslipidemic patients.Molecular and cellular biochemistry · 2018Trial
- Plscr1 inhibits murine norovirus entry.bioRxiv : the preprint server for biology · 2026Article
- Membrane Stress and Ferroptosis: Lipid Dynamics in Cancer.International journal of molecular sciences · 2026Review
- PLSCR1 Regulates the Physiology of Fibroblast-Like Synoviocytes via Modulating the STAT1 Signaling Pathway.Immunity, inflammation and disease · 2025Article
- Article
- Review
- Desipramine induces eryptosis in human erythrocytes, an effect blunted by nitric oxide donor sodium nitroprusside and N-acetyl-L-cysteine but enhanced by Calcium depletion.Cell cycle (Georgetown, Tex.) · 2023Article
- Membrane Lipids in Ultra-High-Risk Patients: Potential Predictive Biomarkers of Conversion to Psychosis.Nutrients · 2023Article
- The enemy within: lipid asymmetry in intracellular parasite-host interactions.Emerging topics in life sciences · 2023Review
- Surface cholesterol-enriched domains specifically promote invasion of breast cancer cell lines by controlling invadopodia and extracellular matrix degradation.Cellular and molecular life sciences : CMLS · 2022Article
- Membrane Cholesterol Enrichment of Red Blood Cell-Derived Microparticles Results in Prolonged Circulation.ACS applied bio materials · 2022Article
- The ratio of ATP11C/PLSCR1 mRNA transcripts has clinical significance in sickle cell anemia.Annals of hematology · 2022Article
- The role of cholesterol in invasion and growth of malaria parasites.Frontiers in cellular and infection microbiology · 2022Review
- Alteration of cholesterol distribution at the plasma membrane of cancer cells: From evidence to pathophysiological implication and promising therapy strategy.Frontiers in physiology · 2022Review
- Of membranes and malaria: phospholipid asymmetry in Plasmodium falciparum-infected red blood cells.Cellular and molecular life sciences : CMLS · 2021Review
- Identification and characterisation of a phospholipid scramblase in the malaria parasite Plasmodium falciparum.Molecular and biochemical parasitology · 2021Article
- Proteostasis of Islet Amyloid Polypeptide: A Molecular Perspective of Risk Factors and Protective Strategies for Type II Diabetes.Chemical reviews · 2021Review
- Breakdown in membrane asymmetry regulation leads to monocyte recognition of P. falciparum-infected red blood cells.PLoS pathogens · 2021Article
- Molecular Basis of the Anticancer and Antibacterial Properties of CecropinXJ Peptide: An In Silico Study.International journal of molecular sciences · 2021Article
- Reduction in flippase activity contributes to surface presentation of phosphatidylserine in human senescent erythrocytes.Journal of cellular and molecular medicine · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
An asymmetric distribution of phospholipids in the membrane bilayer is inseparable from physiological functions, including shape preservation and survival of erythrocytes, and by implication other cells. Aminophospholipids, notably phosphatidylserine (PS), are confined to the inner leaflet of the erythrocyte membrane lipid bilayer by the ATP-dependent flippase enzyme, ATP11C, counteracting the activity of an ATP-independent scramblase. Phospholipid scramblase 1 (PLSCR1), a single-transmembrane protein, was previously reported to possess scrambling activity in erythrocytes. However, its function was cast in doubt by the retention of scramblase activity in erythrocytes of knockout mice lacking this protein. We show that in the human erythrocyte PLSCR1 is the predominant scramblase and by reconstitution into liposomes that its activity resides in the transmembrane domain. At or below physiological intracellular calcium concentrations, total suppression of flippase activity nevertheless leaves the membrane asymmetry undisturbed. When liposomes or erythrocytes are depleted of cholesterol (a reversible process in the case of erythrocytes), PS quickly appears at the outer surface, implying that cholesterol acts in the cell as a powerful scramblase inhibitor. Thus, our results bring to light a previously unsuspected function of cholesterol in regulating phospholipid scrambling.
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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.