TORC1 Inhibits GSK3-Mediated Elo2 Phosphorylation to Regulate Very Long Chain Fatty Acid Synthesis and Autophagy

Article Article scientifique Article TORC1 Inhibits GSK3-Mediated Elo2 Phosphorylation to Regulate Very Long Chain Fatty Acid Synthesis and Autophagy eng 2013 author Zimmermann Christine 56373 author Santos De Almeida Aline 750875 author Gable Kenneth author Epstein Sharon 653155 author Gururaj Charulatha author Chymkowitch Pierre author Pultz Dennis author Rødkær Steven V. author Clay Lorena author Bjørås Magnar author Barral Yves author Chang Amy author Færgeman Nils J. author Dunn Teresa M. author Riezman Howard 134430 author Enserink Jorrit M. 1036-1046 10.1016/j.celrep.2013.10.024 2211-1247 https://linkinghub.elsevier.com/retrieve/pii/S2211124713006086 Very long chain fatty acids (VLCFAs) are essential fatty acids with multiple functions, including ceramide synthesis. Although the components of the VLCFA biosynthetic machinery have been elucidated, how their activity is regulated to meet the cell's metabolic demand remains unknown. The goal of this study was to identify mechanisms that regulate the rate of VLCFA synthesis, and we discovered that the fatty acid elongase Elo2 is regulated by phosphorylation. Elo2 phosphorylation is induced upon inhibition of TORC1 and requires GSK3. Expression of nonphosphorylatable Elo2 profoundly alters the ceramide spectrum, reflecting aberrant VLCFA synthesis. Furthermore, VLCFA depletion results in constitutive activation of autophagy, which requires sphingoid base phosphorylation. This constitutive activation of autophagy diminishes cell survival, indicating that VLCFAs serve to dampen the amplitude of autophagy. Together, our data reveal a function for TORC1 and GSK3 in the regulation of VLCFA synthesis that has important implications for autophagy and cell homeostasis. Dewey 540 39 Département de biochimie 144 false Cell Reports 5 4 076374ac-a233-4b2d-a785-c7823fcbe50c Article (Published version) Public Torc1_HR_13.pdf 2036239 application/pdf openAccess Faculté des sciences / Section de chimie et biochimie / Département de biochimie

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TORC1 Inhibits GSK3-Mediated Elo2 Phosphorylation to Regulate Very Long Chain Fatty Acid Synthesis and Autophagy	Cell Reports			2013	234	190

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Zimmermann, Christine