The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
Autophagy Regulates Cholesterol Efflux from Macrophage Foam Cells via Lysosomal Acid Lipase
Open accessAbstract
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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“Bone marrow transfer has been used to document in vivo the role of autophagy in the reverse cholesterol transport pathway from peripheral tissues or cells (e.g., macrophages) to the liver for secretion in bile and for excretion, 638”
From Guidelines for the use and interpretation of assays for monitoring autophagy (2012) · cites this paper as [638]
Experimental — accuracy not yet measuredIn the citing paper
“Uptake of modified lipoproteins, such as oxLDL, has been shown in cultured macrophages to induce autophagy168, apoptosis170, pyroptosis (via induction of NRLP3 inflammasome activation72) and necroptosis169.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [168]
In the citing paper
“| Atherosclerosis | Macrophage‐specific deletion of Atg5 | Enhanced atherogenic plaque progression due to hyperactivation of macrophage‐mediated inflammation and impaired lipid droplets catabolism | Ouimet et al (2011), Liao et al (2012), Razani et al (2012) |”
From Autophagy in major human diseases (2021) · cites this paper as Ouimet et al (2011)
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LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5720 · Cited by 6,605
Autophagy regulates lipid metabolism
Singh, R., Kaushik, S., Wang, Y., Xiang, Y., Novak, I., Komatsu, M., Tanaka, K., Cuervo, A. M., & Czaja, M. J. (2009) · Nature · doi:10.1038/nature07976 · Cited by 3,975
Goldstein, J. L., Ho, Y. K., Basu, S. K., & Brown, M. S. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.1.333 · Cited by 2,447
Dissection of Autophagosome Formation Using Apg5-Deficient Mouse Embryonic Stem Cells
Mizushima, N., Yamamoto, A., Hatano, M., Kobayashi, Y., Kabeya, Y., Suzuki, K., Tokuhisa, T., Ohsumi, Y., & Yoshimori, T. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.4.657 · Cited by 1,361
MiR-33 Contributes to the Regulation of Cholesterol Homeostasis
Rayner, K. J., Suárez, Y., Dávalos, A., Parathath, S., Fitzgerald, M. L., Tamehiro, N., Fisher, E. A., Moore, K. J., & Fernández-Hernando, C. (2010) · Science · doi:10.1126/science.1189862 · Cited by 1,260
Lysosomal turnover, but not a cellular level, of endogenous LC3 is a marker for autophagy
Tanida, I., Minematsu-Ikeguchi, N., Ueno, T., & Kominami, E. (2005) · Autophagy · doi:10.4161/auto.1.2.1697 · Cited by 1,108 · cited 1×
“A further increase in LC3-II protein upon lysosomal inhibition was observed, indicative of a functional autophagic flux in these cells, as cellular LC3 levels per se are not a good marker for autophagy (Tanida et al., 2005).”
Lipid Droplets Finally Get a Little R-E-S-P-E-C-T
Farese, R. V., & Walther, T. C. (2009) · Cell · doi:10.1016/j.cell.2009.11.005 · Cited by 1,047
Basu, S. K., Goldstein, J. L., Anderson, G. W., & Brown, M. S. (1976) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.73.9.3178 · Cited by 1,019
The molecular machinery of autophagy: unanswered questions
Klionsky, D. J. (2004) · Journal of Cell Science · doi:10.1242/jcs.01620 · Cited by 960
Autophagy regulates adipose mass and differentiation in mice
Singh, R., Xiang, Y., Wang, Y., Baikati, K., Cuervo, A. M., Luu, Y. K., Tang, Y., Pessin, J. E., Schwartz, G. J., & Czaja, M. J. (2009) · Journal of Clinical Investigation · doi:10.1172/jci39228 · Cited by 765
Cited by
Sorted by citations
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894
Guidelines for the use and interpretation of assays for monitoring autophagy
Klionsky, D. J., Abdalla, F. C., Abeliovich, H., Abraham, R. T., Acevedo-Arozena, A., Adeli, K., Agholme, L., Agnello, M., Agostinis, P., Aguirre-Ghiso, J. A., et al. (2012) · Autophagy · doi:10.4161/auto.19496 · Cited by 3,996
Macrophages in atherosclerosis: a dynamic balance
Moore, K. J., Sheedy, F. J., & Fisher, E. A. (2013) · Nature reviews. Immunology · doi:10.1038/nri3520 · Cited by 2,559
Lipid Droplets and Cellular Lipid Metabolism
Walther, T. C., & Farese, R. V. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061009-102430 · Cited by 1,701
Autophagy in major human diseases
Klionsky, D. J., Petroni, G., Amaravadi, R. K., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cadwell, K., Cecconi, F., Choi, A. M. K., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2021108863 · Cited by 1,585
Metadata
- 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.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 13
- Issue
- 6
- Pages
- 655-667
- ISSN
- 1550-4131 (ISSN-L)
- 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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