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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Main Authors: Aikaterini Alexaki, Sita D. Gupta, Saurav Majumder, Mari Kono, Galina Tuymetova, Jeffrey M. Harmon, Teresa M. Dunn, Richard L. Proia
Format: Article
Language:English
Published: Elsevier 2014-12-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S002222752036692X
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spelling 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
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