Autophagy regulates sphingolipid levels in the liver[S]
Sphingolipid levels are tightly regulated to maintain cellular homeostasis. During pathologic conditions such as in aging, inflammation, and metabolic and neurodegenerative diseases, levels of some sphingolipids, including the bioactive metabolite ceramide, are elevated. Sphingolipid metabolism has...
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doaj-b14df911e5c248649fe18fc4222221902021-04-28T06:01:15ZengElsevierJournal of Lipid Research0022-22752014-12-01551225212531Autophagy regulates sphingolipid levels in the liver[S]Aikaterini Alexaki0Sita D. Gupta1Saurav Majumder2Mari Kono3Galina Tuymetova4Jeffrey M. Harmon5Teresa M. Dunn6Richard L. Proia7Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892Departments of Biochemistry Uniformed Services University of the Health Sciences, Bethesda, MD 20184Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892Molecular Biology and Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD 20184Departments of Biochemistry Uniformed Services University of the Health Sciences, Bethesda, MD 20184To whom correspondence should be addressed; Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892; To whom correspondence should be addressedSphingolipid levels are tightly regulated to maintain cellular homeostasis. During pathologic conditions such as in aging, inflammation, and metabolic and neurodegenerative diseases, levels of some sphingolipids, including the bioactive metabolite ceramide, are elevated. Sphingolipid metabolism has been linked to autophagy, a critical catabolic process in both normal cell function and disease; however, the in vivo relevance of the interaction is not well-understood. Here, we show that blocking autophagy in the liver by deletion of the Atg7 gene, which is essential for autophagosome formation, causes an increase in sphingolipid metabolites including ceramide. We also show that overexpression of serine palmitoyltransferase to elevate de novo sphingolipid biosynthesis induces autophagy in the liver. The results reveal autophagy as a process that limits excessive ceramide levels and that is induced by excessive elevation of de novo sphingolipid synthesis in the liver. Dysfunctional autophagy may be an underlying mechanism causing elevations in ceramide that may contribute to pathogenesis in diseases.http://www.sciencedirect.com/science/article/pii/S002222752036692Xceramidelipidsendoplasmic reticulumtriglycerideslipophagy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aikaterini Alexaki Sita D. Gupta Saurav Majumder Mari Kono Galina Tuymetova Jeffrey M. Harmon Teresa M. Dunn Richard L. Proia |
spellingShingle |
Aikaterini Alexaki Sita D. Gupta Saurav Majumder Mari Kono Galina Tuymetova Jeffrey M. Harmon Teresa M. Dunn Richard L. Proia Autophagy regulates sphingolipid levels in the liver[S] Journal of Lipid Research ceramide lipids endoplasmic reticulum triglycerides lipophagy |
author_facet |
Aikaterini Alexaki Sita D. Gupta Saurav Majumder Mari Kono Galina Tuymetova Jeffrey M. Harmon Teresa M. Dunn Richard L. Proia |
author_sort |
Aikaterini Alexaki |
title |
Autophagy regulates sphingolipid levels in the liver[S] |
title_short |
Autophagy regulates sphingolipid levels in the liver[S] |
title_full |
Autophagy regulates sphingolipid levels in the liver[S] |
title_fullStr |
Autophagy regulates sphingolipid levels in the liver[S] |
title_full_unstemmed |
Autophagy regulates sphingolipid levels in the liver[S] |
title_sort |
autophagy regulates sphingolipid levels in the liver[s] |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2014-12-01 |
description |
Sphingolipid levels are tightly regulated to maintain cellular homeostasis. During pathologic conditions such as in aging, inflammation, and metabolic and neurodegenerative diseases, levels of some sphingolipids, including the bioactive metabolite ceramide, are elevated. Sphingolipid metabolism has been linked to autophagy, a critical catabolic process in both normal cell function and disease; however, the in vivo relevance of the interaction is not well-understood. Here, we show that blocking autophagy in the liver by deletion of the Atg7 gene, which is essential for autophagosome formation, causes an increase in sphingolipid metabolites including ceramide. We also show that overexpression of serine palmitoyltransferase to elevate de novo sphingolipid biosynthesis induces autophagy in the liver. The results reveal autophagy as a process that limits excessive ceramide levels and that is induced by excessive elevation of de novo sphingolipid synthesis in the liver. Dysfunctional autophagy may be an underlying mechanism causing elevations in ceramide that may contribute to pathogenesis in diseases. |
topic |
ceramide lipids endoplasmic reticulum triglycerides lipophagy |
url |
http://www.sciencedirect.com/science/article/pii/S002222752036692X |
work_keys_str_mv |
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1721504624092905472 |