Cited by 779Cholesterol and Lipid MetabolismAutophagy in Disease and TherapyLipid metabolism and biosynthesis

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Autophagy Regulates Cholesterol Efflux from Macrophage Foam Cells via Lysosomal Acid Lipase

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Ouimet, Mireille, Franklin, Vivian, Mak, Esther, Liao, Xianghai, Tabas, Ira, Marcel, Yves L.·2011·Cell Metabolism

DOI 10.1016/j.cmet.2011.03.023PMC PMC3257518

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Abstract

The lipid droplet (LD) is the major site of cholesterol storage in macrophage foam cells and is a potential therapeutic target for the treatment of atherosclerosis. Cholesterol, stored as cholesteryl esters (CEs), is liberated from this organelle and delivered to cholesterol acceptors. The current paradigm attributes all cytoplasmic CE hydrolysis to the action of neutral CE hydrolases. Here, we demonstrate an important role for lysosomes in LD CE hydrolysis in cholesterol-loaded macrophages, in addition to that mediated by neutral hydrolases. Furthermore, we demonstrate that LDs are delivered to lysosomes via autophagy, where lysosomal acid lipase (LAL) acts to hydrolyze LD CE to generate free cholesterol mainly for ABCA1-dependent efflux; this process is specifically induced upon macrophage cholesterol loading. We conclude that, in macrophage foam cells, lysosomal hydrolysis contributes to the mobilization of LD-associated cholesterol for reverse cholesterol transport.

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Authors: Ouimet, M., Franklin, V., Mak, E., Liao, X., Tabas, I., & Marcel, Y. L.
Affiliations: University of Ottawa (CA)
Ottawa Heart Institute (CA)
Columbia University (US)
Corresponding author: Marcel, Yves L.
ORCID: Ouimet, Mireille
Mak, Esther
Tabas, Ira
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2011-06
Volume: 13
Issue: 6
Pages: 655-667
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2011.03.023
PMC: PMC3257518
OpenAlex: W1983619827
Cited by: 774
References: 57
Citations by year: 2026: 49 · 2025: 57 · 2024: 42 · 2023: 61 · 2022: 61 · 2021: 69 · 2020: 62 · 2019: 48 · 2018: 66 · 2017: 52 · 2016: 51 · 2015: 48 · 2014: 35 · 2013: 28 · 2012: 37
FWCI: 34.74
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 813 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Canadian Institutes of Health Research
Heart and Stroke Foundation of Canada
National Institutes of Health (HL057560)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords: autophagy, lysosomal acid lipase, foam cells, cholesterol efflux, lipid droplets, cholesterol ester hydrolysis, lysosomes, ABCA1, reverse cholesterol transport, atherosclerosis, free cholesterol
MeSH terms: Autophagy-Related Protein 5, Animals, Autophagy, Bone Marrow Cells, Cells, Cultured, Chloroquine, Cholesterol, Sterol Esterase, Foam Cells, Lipolysis, Lipoproteins, LDL, Lysosomes, Mice, Inbred C57BL, Microtubule-Associated Proteins, Paraoxon, Mice, Knockout, Atherosclerosis, Lipid Metabolism, Mice, Gene Knockout Techniques

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Autophagy Regulates Cholesterol Efflux from Macrophage Foam Cells via Lysosomal Acid Lipase

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