title: AMPK and vacuole-associated Atg14p orchestrate μ-lipophagy for energy production and long-term survival under glucose starvation.
abstract: Dietary restriction increases the longevity of many organisms, but the cell signaling and organellar mechanisms underlying this capability are unclear. We demonstrate that to permit long-term survival in response to sudden glucose depletion, yeast cells activate lipid-droplet (LD) consumption through micro-lipophagy (µ-lipophagy), in which fat is metabolized as an alternative energy source. AMP-activated protein kinase (AMPK) activation triggered this pathway, which required Atg14p. More gradual glucose starvation, amino acid deprivation or rapamycin did not trigger µ-lipophagy and failed to provide the needed substitute energy source for long-term survival. During acute glucose restriction, activated AMPK was stabilized from degradation and interacted with Atg14p. This prompted Atg14p redistribution from ER exit sites onto liquid-ordered vacuole membrane domains, initiating µ-lipophagy. Our findings that activated AMPK and Atg14p are required to orchestrate µ-lipophagy for energy production in starved cells is relevant for studies on aging and evolutionary survival strategies of different organisms.
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.|Cell Biology and Metabolism Program, National Institutes of Health, Bethesda, United States.
authors.forename: Arnold Y
authors.identifier: 0000-0002-4607-8925
authors.initials: AY
authors.lastname: Seo
authors.affiliation: Cell Biology and Metabolism Program, National Institutes of Health, Bethesda, United States.
authors.forename: Pick-Wei
authors.initials: PW
authors.lastname: Lau
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.|Cell Biology and Metabolism Program, National Institutes of Health, Bethesda, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Feliciano
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.|Cell Biology and Metabolism Program, National Institutes of Health, Bethesda, United States.
authors.forename: Prabuddha
authors.initials: P
authors.lastname: Sengupta
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, United States.|Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, United States.
authors.forename: Mark A Le
authors.initials: MAL
authors.lastname: Gros
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, United States.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Cinquin
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, United States.|Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, United States.
authors.forename: Carolyn A
authors.identifier: 0000-0002-6262-4789
authors.initials: CA
authors.lastname: Larabell
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.|Cell Biology and Metabolism Program, National Institutes of Health, Bethesda, United States.
authors.forename: Jennifer
authors.identifier: 0000-0002-8601-3501
authors.initials: J
authors.lastname: Lippincott-Schwartz
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D001343:Autophagy; D000071183:Autophagy-Related Proteins / Q000378:metabolism*; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism*; D050356:Lipid Metabolism; D050296:Microbial Viability; D011494:Protein Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: C114337:ATG 14 protein, S cerevisiae; D000071183:Autophagy-Related Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D005947:Glucose
keywords: AMPK; ATG14; S. cerevisiae; cell biology; lipid-droplets; microautophagy; starvation-induced lifespan extension; vacuole-membrane domains