title: A defect of the vacuolar putative lipase Atg15 accelerates degradation of lipid droplets through lipolysis.
abstract: Lipid droplets (LDs) are the conserved organelles for the deposit of neutral lipids, and function as reservoirs of membrane and energy sources. To date, functional links between autophagy and LD dynamics have not been fully elucidated. Here, we report that a vacuolar putative lipase, Atg15, required for degradation of autophagic bodies, is crucial for the maintenance of LD amount in the yeast Saccharomyces cerevisiae in the stationary phase. Mutant analyses revealed that the putative lipase motif and vacuolar localization of Atg15 are important for the maintenance of LD amount. Loss of autophagosome formation by simultaneous deletion of core ATG genes cancelled the reduction in the LD amount in ATG15-deleted cells, indicating that degradation of autophagic bodies accounts for the functional involvement of Atg15 in LD dynamics. The reduced level of LDs in the mutant strain was dependent on Tgl3 and Tgl4, major lipases for lipolysis in S. cerevisiae. An altered phosphorylation status of Tgl3, higher accumulation of Tgl4, and closer associations of Tgl3 and Tgl4 with LDs were detected in the ATG15-deleted cells. Furthermore, increased levels of downstream metabolites of lipolysis in the mutant strain strongly suggested enhanced lipolytic activity caused by loss of ATG15. Our data provide evidence for a novel link between autophagic flux and LD dynamics integrated with Atg15 activity.
authors.affiliation: a Division of Applied Life Sciences; Graduate School of Agriculture; Research Unit for Physiological Chemistry; Center for the Promotion of Interdisciplinary Education and Research; Kyoto University; Kitashirakawa-Oiwake ; Sakyo , Kyoto Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Maeda
authors.forename: Masahide
authors.initials: M
authors.lastname: Oku
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Sakai
mesh_terms: D020816:Amino Acid Motifs; D000071183:Autophagy-Related Proteins; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry / Q000502:physiology*; D002470:Cell Survival; D003593:Cytoplasm / Q000378:metabolism; D017353:Gene Deletion; D008049:Lipase / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D008066:Lipolysis; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000502:physiology*; D008856:Microscopy, Fluorescence; D009154:Mutation; D010641:Phenotype; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000502:physiology*; D014617:Vacuoles / Q000737:chemistry
chemical_list: D000071183:Autophagy-Related Proteins; D008055:Lipids; D008562:Membrane Glycoproteins; D029701:Saccharomyces cerevisiae Proteins; C423315:ATG15 protein, S cerevisiae; D002265:Carboxylic Ester Hydrolases; D008049:Lipase; C476342:TGL3 protein, S cerevisiae; C506904:Tgl4 protein, S cerevisiae
keywords: Atg15; Tgl3; Tgl4; autophagy; lipid droplet; lipolysis; triacylglycerol