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Autophagy regulates sphingolipid levels in the liver.


ABSTRACT: 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.

SUBMITTER: Alexaki A 

PROVIDER: S-EPMC4242445 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Autophagy regulates sphingolipid levels in the liver.

Alexaki Aikaterini A   Gupta Sita D SD   Majumder Saurav S   Kono Mari M   Tuymetova Galina G   Harmon Jeffrey M JM   Dunn Teresa M TM   Proia Richard L RL  

Journal of lipid research 20141020 12


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 a  ...[more]

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