title: Role for Lipid Droplet Biogenesis and Microlipophagy in Adaptation to Lipid Imbalance in Yeast.
abstract: The immediate responses to inhibition of phosphatidylcholine (PC) biosynthesis in yeast are altered phospholipid levels, slow growth, and defects in the morphology and localization of ER and mitochondria. With chronic lipid imbalance, yeast adapt. Lipid droplet (LD) biogenesis and conversion of phospholipids to triacylglycerol are required for restoring some phospholipids to near-wild-type levels. We confirmed that the unfolded protein response is activated by this lipid stress and find that Hsp104p is recruited to ER aggregates. We also find that LDs form at ER aggregates, contain polyubiquitinated proteins and an ER chaperone, and are degraded in the vacuole by a process resembling microautophagy. This process, microlipophagy, is required for restoration of organelle morphology and cell growth during adaptation to lipid stress. Microlipophagy does not require ATG7 but does requires ESCRT components and a newly identified class E VPS protein that localizes to ER and is upregulated by lipid imbalance.
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, 630 West 168(th) Street, New York, NY 10032, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Vevea
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, 630 West 168(th) Street, New York, NY 10032, USA.
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: Garcia
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, 630 West 168(th) Street, New York, NY 10032, USA.
authors.forename: Robin B
authors.initials: RB
authors.lastname: Chan
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, 630 West 168(th) Street, New York, NY 10032, USA.
authors.forename: Bowen
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, 630 West 168(th) Street, New York, NY 10032, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Schultz
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, 630 West 168(th) Street, New York, NY 10032, USA.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Di Paolo
authors.affiliation: Integrated Imaging Center, Department of Biology, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
authors.forename: J Michael
authors.initials: JM
authors.lastname: McCaffery
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, 630 West 168(th) Street, New York, NY 10032, USA. Electronic address: lap5@cumc.columbia.edu.
authors.forename: Liza A
authors.initials: LA
authors.lastname: Pon
mesh_terms: D001343:Autophagy; D000071193:Autophagy-Related Protein 7; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D066292:Lipid Droplets / Q000737:chemistry*; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000737:chemistry; D050918:Phosphatidylethanolamine N-Methyltransferase / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D017423:Sequence Analysis, RNA; D025801:Ubiquitin / Q000737:chemistry; D056811:Unfolded Protein Response; D014617:Vacuoles / Q000378:metabolism
chemical_list: C114830:ATG7 protein, S cerevisiae; D056827:Endosomal Sorting Complexes Required for Transport; D010713:Phosphatidylcholines; D010743:Phospholipids; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D049452:Green Fluorescent Proteins; C494486:CHO2 protein, S cerevisiae; D050918:Phosphatidylethanolamine N-Methyltransferase; D000071193:Autophagy-Related Protein 7