title: Lipid droplets and their component triglycerides and steryl esters regulate autophagosome biogenesis.
abstract: Autophagy is a major catabolic process responsible for the delivery of proteins and organelles to the lysosome/vacuole for degradation. Malfunction of this pathway has been implicated in numerous pathological conditions. Different organelles have been found to contribute to the formation of autophagosomes, but the exact mechanism mediating this process remains obscure. Here, we show that lipid droplets (LDs) are important for the regulation of starvation-induced autophagy. Deletion of Dga1 and Lro1 enzymes responsible for triacylglycerol (TAG) synthesis, or of Are1 and Are2 enzymes responsible for the synthesis of steryl esters (STE), results in the inhibition of autophagy. Moreover, we identified the STE hydrolase Yeh1 and the TAG lipase Ayr1 as well as the lipase/hydrolase Ldh1 as essential for autophagy. Finally, we provide evidence that the ER-LD contact-site proteins Ice2 and Ldb16 regulate autophagy. Our study thus highlights the importance of lipid droplet dynamics for the autophagic process under nitrogen starvation.
authors.affiliation: Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Tomer
authors.initials: T
authors.lastname: Shpilka
authors.affiliation: Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Welter
authors.affiliation: Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Borovsky
authors.affiliation: Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Nira
authors.initials: N
authors.lastname: Amar
authors.affiliation: Department of Cell Biology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Muriel
authors.initials: M
authors.lastname: Mari
authors.affiliation: Department of Cell Biology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Reggiori
authors.affiliation: Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel zvulun.elazar@weizmann.ac.il.
authors.forename: Zvulun
authors.initials: Z
authors.lastname: Elazar
mesh_terms: D001343:Autophagy; D004952:Esters / Q000378:metabolism*; D066292:Lipid Droplets / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D010588:Phagosomes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D004952:Esters; D014280:Triglycerides
keywords: Atg8; autophagosome biogenesis; autophagy; fatty acid synthase; lipid droplets