AMPK and vacuole-associated Atg14p orchestrate μ-lipophagy for energy production and long-term survival under glucose starvation

Seo, Arnold Y.; Lau, Pick-Wei; Feliciano, Daniel; Sengupta, Prabuddha; Gros, Mark A. Le; Cinquin, Bertrand; Larabell, Carolyn A.; Lippincott-Schwartz, Jennifer

doi:10.7554/eLife.21690

Title: AMPK and vacuole-associated Atg14p orchestrate μ-lipophagy for energy production and long-term survival under glucose starvation

Journal Article · Mon Apr 10 00:00:00 EDT 2017 · eLife

DOI:https://doi.org/10.7554/eLife.21690· OSTI ID:1351057

^[1]; Lau, Pick-Wei ^[2]; Feliciano, Daniel ^[1]; Sengupta, Prabuddha ^[1]; Gros, Mark A. Le ^[3]; Cinquin, Bertrand ^[4];

^[3];

^[1]

Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States, Cell Biology and Metabolism Program, National Institutes of Health, Bethesda, United States
Cell Biology and Metabolism Program, National Institutes of Health, Bethesda, United States
Department of Anatomy, University of California, San Francisco, San Francisco, United States, Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, United States
Department of Anatomy, University of California, San Francisco, San Francisco, United States

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.

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Research Organization:: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-5CH11231; AC02-05CH11231

OSTI ID:: 1351057

Alternate ID(s):: OSTI ID: 1351058; OSTI ID: 1379802

Journal Information:: eLife, Journal Name: eLife Vol. 6; ISSN 2050-084X

Publisher:: eLife Sciences Publications, Ltd.Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 93 works

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References (58)

Apg14p and Apg6/Vps30p Form a Protein Complex Essential for Autophagy in the Yeast, Saccharomyces cerevisiae Kametaka, Satoshi; Okano, Takafumi; Ohsumi, Mariko Journal of Biological Chemistry, Vol. 273, Issue 35 https://doi.org/10.1074/jbc.273.35.22284	journal	August 1998
New insights into the role of mitochondria in aging: mitochondrial dynamics and more Seo, A. Y.; Joseph, A. -M.; Dutta, D. Journal of Cell Science, Vol. 123, Issue 15 https://doi.org/10.1242/jcs.070490	journal	July 2010
Golgi Structure Correlates with Transitional Endoplasmic Reticulum Organization in Pichia pastoris and Saccharomyces cerevisiae Rossanese, Olivia W.; Soderholm, Jon; Bevis, Brooke J. The Journal of Cell Biology, Vol. 145, Issue 1 https://doi.org/10.1083/jcb.145.1.69	journal	April 1999
Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans Greer, Eric L.; Brunet, Anne Aging Cell, Vol. 8, Issue 2 https://doi.org/10.1111/j.1474-9726.2009.00459.x	journal	April 2009
Lipid droplet autophagy in the yeast Saccharomyces cerevisiae van Zutphen, Tim; Todde, Virginia; de Boer, Rinse Molecular Biology of the Cell, Vol. 25, Issue 2 https://doi.org/10.1091/mbc.E13-08-0448	journal	January 2014
Membrane Recruitment of Aut7p in the Autophagy and Cytoplasm to Vacuole Targeting Pathways Requires Aut1p, Aut2p, and the Autophagy Conjugation Complex Kim, John; Huang, Wei-Pang; Klionsky, Daniel J. The Journal of Cell Biology, Vol. 152, Issue 1 https://doi.org/10.1083/jcb.152.1.51	journal	January 2001
An Overview of Autophagy: Morphology, Mechanism, and Regulation Parzych, Katherine R.; Klionsky, Daniel J. Antioxidants & Redox Signaling, Vol. 20, Issue 3 https://doi.org/10.1089/ars.2013.5371	journal	January 2014
mTOR inhibition activates overall protein degradation by the ubiquitin proteasome system as well as by autophagy Zhao, Jinghui; Zhai, Bo; Gygi, Steven P. Proceedings of the National Academy of Sciences, Vol. 112, Issue 52 https://doi.org/10.1073/pnas.1521919112	journal	December 2015
Dietary Restriction Depends on Nutrient Composition to Extend Chronological Lifespan in Budding Yeast Saccharomyces cerevisiae Wu, Ziyun; Liu, Shao Quan; Huang, Dejian PLoS ONE, Vol. 8, Issue 5 https://doi.org/10.1371/journal.pone.0064448	journal	May 2013
Atg38 is required for autophagy-specific phosphatidylinositol 3-kinase complex integrity Araki, Yasuhiro; Ku, Wei-Chi; Akioka, Manami The Journal of Cell Biology, Vol. 203, Issue 2 https://doi.org/10.1083/jcb.201304123	journal	October 2013
Mitochondria Autophagy in Yeast Kanki, Tomotake; Klionsky, Daniel J.; Okamoto, Koji Antioxidants & Redox Signaling, Vol. 14, Issue 10 https://doi.org/10.1089/ars.2010.3762	journal	May 2011
Autophagy regulates lipid metabolism Singh, Rajat; Kaushik, Susmita; Wang, Yongjun Nature, Vol. 458, Issue 7242 https://doi.org/10.1038/nature07976	journal	April 2009
ER-phagy mediates selective degradation of endoplasmic reticulum independently of the core autophagy machinery Schuck, S.; Gallagher, C. M.; Walter, P. Journal of Cell Science, Vol. 127, Issue 18 https://doi.org/10.1242/jcs.154716	journal	July 2014
Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening Liao, Chen-Yu; Rikke, Brad A.; Johnson, Thomas E. Aging Cell, Vol. 9, Issue 1 https://doi.org/10.1111/j.1474-9726.2009.00533.x	journal	February 2010
Autophagy and amino acid homeostasis are required for chronological longevity in Saccharomyces cerevisiae Alvers, Ashley L.; Fishwick, Laura K.; Wood, Michael S. Aging Cell, Vol. 8, Issue 4 https://doi.org/10.1111/j.1474-9726.2009.00469.x	journal	August 2009
Calorie Restriction: Is AMPK a Key Sensor and Effector? Cantó, Carles; Auwerx, Johan Physiology, Vol. 26, Issue 4 https://doi.org/10.1152/physiol.00010.2011	journal	August 2011
The Role of Atg Proteins in Autophagosome Formation Mizushima, Noboru; Yoshimori, Tamotsu; Ohsumi, Yoshinori Annual Review of Cell and Developmental Biology, Vol. 27, Issue 1 https://doi.org/10.1146/annurev-cellbio-092910-154005	journal	November 2011
Selective autophagy in budding yeast Suzuki, Kuninori Cell Death & Differentiation, Vol. 20, Issue 1 https://doi.org/10.1038/cdd.2012.73	journal	June 2012
FAT SIGNALS - Lipases and Lipolysis in Lipid Metabolism and Signaling Zechner, Rudolf; Zimmermann, Robert; Eichmann, Thomas O. Cell Metabolism, Vol. 15, Issue 3 https://doi.org/10.1016/j.cmet.2011.12.018	journal	March 2012
Quantitative analysis of yeast internal architecture using soft X-ray tomography Uchida, Maho; Sun, Yidi; McDermott, Gerry Yeast, Vol. 28, Issue 3 https://doi.org/10.1002/yea.1834	journal	December 2010
Lipid droplet–mediated ER homeostasis regulates autophagy and cell survival during starvation Velázquez, Ariadna P.; Tatsuta, Takashi; Ghillebert, Ruben The Journal of Cell Biology, Vol. 212, Issue 6 https://doi.org/10.1083/jcb.201508102	journal	March 2016
An AMPK-FOXO Pathway Mediates Longevity Induced by a Novel Method of Dietary Restriction in C. elegans Greer, Eric L.; Dowlatshahi, Dara; Banko, Max R. Current Biology, Vol. 17, Issue 19 https://doi.org/10.1016/j.cub.2007.08.047	journal	October 2007
Microautophagy of the Nucleus Coincides with a Vacuolar Diffusion Barrier at Nuclear–Vacuolar Junctions Dawaliby, Rosie; Mayer, Andreas Molecular Biology of the Cell, Vol. 21, Issue 23 https://doi.org/10.1091/mbc.E09-09-0782	journal	December 2010
Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys Colman, Ricki J.; Beasley, T. Mark; Kemnitz, Joseph W. Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms4557	journal	April 2014
Autophagy and leucine promote chronological longevity and respiration proficiency during calorie restriction in yeast Aris, John P.; Alvers, Ashley L.; Ferraiuolo, Roy A. Experimental Gerontology, Vol. 48, Issue 10 https://doi.org/10.1016/j.exger.2013.01.006	journal	October 2013
Effect of calorie restriction on the metabolic history of chronologically aging yeast Goldberg, Alexander A.; Bourque, Simon D.; Kyryakov, Pavlo Experimental Gerontology, Vol. 44, Issue 9 https://doi.org/10.1016/j.exger.2009.06.001	journal	September 2009
Functional Characterization of the S. cerevisiae Genome by Gene Deletion and Parallel Analysis Winzeler, E. A. Science, Vol. 285, Issue 5429 https://doi.org/10.1126/science.285.5429.901	journal	August 1999
An intimate collaboration between peroxisomes and lipid bodies Binns, Derk; Januszewski, Tom; Chen, Yue The Journal of Cell Biology, Vol. 173, Issue 5 https://doi.org/10.1083/jcb.200511125	journal	May 2006
Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae Tsukada, Miki; Ohsumi, Yoshinori FEBS Letters, Vol. 333, Issue 1-2 https://doi.org/10.1016/0014-5793(93)80398-E	journal	October 1993
Stationary phase in yeast Herman, Paul K. Current Opinion in Microbiology, Vol. 5, Issue 6 https://doi.org/10.1016/S1369-5274(02)00377-6	journal	December 2002
Tor-Mediated Induction of Autophagy via an Apg1 Protein Kinase Complex Kamada, Yoshiaki; Funakoshi, Tomoko; Shintani, Takahiro The Journal of Cell Biology, Vol. 150, Issue 6 https://doi.org/10.1083/jcb.150.6.1507	journal	September 2000
Glucose regulates protein interactions within the yeast SNF1 protein kinase complex. Jiang, R.; Carlson, M. Genes & Development, Vol. 10, Issue 24 https://doi.org/10.1101/gad.10.24.3105	journal	December 1996
ER exit sites are physical and functional core autophagosome biogenesis components Graef, Martin; Friedman, Jonathan R.; Graham, Christopher Molecular Biology of the Cell, Vol. 24, Issue 18 https://doi.org/10.1091/mbc.E13-07-0381	journal	September 2013
Regulation of Snf1 Kinase: ACTIVATION REQUIRES PHOSPHORYLATION OF THREONINE 210 BY AN UPSTREAM KINASE AS WELL AS A DISTINCT STEP MEDIATED BY THE Snf4 SUBUNIT McCartney, Rhonda R.; Schmidt, Martin C. Journal of Biological Chemistry, Vol. 276, Issue 39 https://doi.org/10.1074/jbc.M104418200	journal	August 2001
Good Fat, Essential Cellular Requirements for Triacylglycerol Synthesis to Maintain Membrane Homeostasis in Yeast Petschnigg, Julia; Wolinski, Heimo; Kolb, Dagmar Journal of Biological Chemistry, Vol. 284, Issue 45, p. 30981-30993 https://doi.org/10.1074/jbc.M109.024752	journal	July 2009
Two Distinct Vps34 Phosphatidylinositol 3–Kinase Complexes Function in Autophagy and Carboxypeptidase Y Sorting in Saccharomyces cerevisiae Kihara, Akio; Noda, Takeshi; Ishihara, Naotada The Journal of Cell Biology, Vol. 152, Issue 3 https://doi.org/10.1083/jcb.152.3.519	journal	January 2001
How to Live Long and Prosper: Autophagy, Mitochondria, and Aging Yen, Wei-Lien; Klionsky, Daniel J. Physiology, Vol. 23, Issue 5 https://doi.org/10.1152/physiol.00013.2008	journal	October 2008
Reduced TOR Signaling Extends Chronological Life Span via Increased Respiration and Upregulation of Mitochondrial Gene Expression Bonawitz, Nicholas D.; Chatenay-Lapointe, Marc; Pan, Yong Cell Metabolism, Vol. 5, Issue 4 https://doi.org/10.1016/j.cmet.2007.02.009	journal	April 2007
Dissection of Autophagosome Biogenesis into Distinct Nucleation and Expansion Steps Abeliovich, Hagai; Dunn, William A.; Kim, John The Journal of Cell Biology, Vol. 151, Issue 5 https://doi.org/10.1083/jcb.151.5.1025	journal	November 2000
Mitochondria-targeted green fluorescent proteins: convenient tools for the study of organelle biogenesis inSaccharomyces cerevisiae Westermann, Benedikt; Neupert, Walter Yeast, Vol. 16, Issue 15 https://doi.org/10.1002/1097-0061(200011)16:15<1421::AID-YEA624>3.0.CO;2-U	journal	January 2000
The ER–Golgi intermediate compartment is a key membrane source for the LC3 lipidation step of autophagosome biogenesis Ge, Liang; Melville, David; Zhang, Min eLife, Vol. 2 https://doi.org/10.7554/eLife.00947	journal	August 2013
Atg14: A Key Player in Orchestrating Autophagy Obara, Keisuke; Ohsumi, Yoshinori International Journal of Cell Biology, Vol. 2011 https://doi.org/10.1155/2011/713435	journal	January 2011
Lipid droplets and their component triglycerides and steryl esters regulate autophagosome biogenesis Shpilka, Tomer; Welter, Evelyn; Borovsky, Noam The EMBO Journal, Vol. 34, Issue 16 https://doi.org/10.15252/embj.201490315	journal	July 2015
Designer deletion strains derived fromSaccharomyces cerevisiae S288C: A useful set of strains and plasmids for PCR-mediated gene disruption and other applications Baker Brachmann, Carrie; Davies, Adrian; Cost, Gregory J. Yeast, Vol. 14, Issue 2 https://doi.org/10.1002/(SICI)1097-0061(19980130)14:2<115::AID-YEA204>3.0.CO;2-2	journal	January 1998
Switching the mode of metabolism in the yeast Saccharomyces cerevisiae Otterstedt, Karin; Larsson, Christer; Bill, Roslyn M. EMBO reports, Vol. 5, Issue 5 https://doi.org/10.1038/sj.embor.7400132	journal	May 2004
Glucose Restriction Extends Caenorhabditis elegans Life Span by Inducing Mitochondrial Respiration and Increasing Oxidative Stress Schulz, Tim J.; Zarse, Kim; Voigt, Anja Cell Metabolism, Vol. 6, Issue 4 https://doi.org/10.1016/j.cmet.2007.08.011	journal	October 2007
Mitochondria and the Autophagy-Inflammation-Cell Death Axis in Organismal Aging Green, D. R.; Galluzzi, L.; Kroemer, G. Science, Vol. 333, Issue 6046 https://doi.org/10.1126/science.1201940	journal	August 2011
Imaging cellular architecture with X-rays Larabell, Carolyn A.; Nugent, Keith A. Current Opinion in Structural Biology, Vol. 20, Issue 5 https://doi.org/10.1016/j.sbi.2010.08.008	journal	October 2010
Neutral Lipid Stores and Lipase PNPLA5 Contribute to Autophagosome Biogenesis Dupont, Nicolas; Chauhan, Santosh; Arko-Mensah, John Current Biology, Vol. 24, Issue 6 https://doi.org/10.1016/j.cub.2014.02.008	journal	March 2014
Calorie restriction extends the chronological lifespan of Saccharomyces cerevisiae independently of the Sirtuins Smith, Jr, Daniel L.; McClure, Julie M.; Matecic, Mirela Aging Cell, Vol. 6, Issue 5 https://doi.org/10.1111/j.1474-9726.2007.00326.x	journal	October 2007
Direct imaging reveals stable, micrometer-scale lipid domains that segregate proteins in live cells Toulmay, Alexandre; Prinz, William A. The Journal of Cell Biology, Vol. 202, Issue 1 https://doi.org/10.1083/jcb.201301039	journal	July 2013
The AMP-Activated Protein Kinase. Fuel Gauge of the Mammalian Cell? Hardie, D. Grahame; Carling, David European Journal of Biochemistry, Vol. 246, Issue 2 https://doi.org/10.1111/j.1432-1033.1997.00259.x	journal	June 1997
Role for Lipid Droplet Biogenesis and Microlipophagy in Adaptation to Lipid Imbalance in Yeast Vevea, Jason D.; Garcia, Enrique J.; Chan, Robin B. Developmental Cell, Vol. 35, Issue 5 https://doi.org/10.1016/j.devcel.2015.11.010	journal	December 2015
A sterol-enriched vacuolar microdomain mediates stationary phase lipophagy in budding yeast Wang, Chao-Wen; Miao, Yu-Hsuan; Chang, Yi-Shun The Journal of Cell Biology, Vol. 206, Issue 3 https://doi.org/10.1083/jcb.201404115	journal	July 2014
Glucose induces cAMP-independent growth-related changes in stationary-phase cells of Saccharomyces cerevisiae. Granot, D.; Snyder, M. Proceedings of the National Academy of Sciences, Vol. 88, Issue 13 https://doi.org/10.1073/pnas.88.13.5724	journal	July 1991
Dynamics and diversity in autophagy mechanisms: lessons from yeast Nakatogawa, Hitoshi; Suzuki, Kuninori; Kamada, Yoshiaki Nature Reviews Molecular Cell Biology, Vol. 10, Issue 7 https://doi.org/10.1038/nrm2708	journal	June 2009
Autophagy is required for extension of yeast chronological life span by rapamycin Alvers, Ashley L.; Wood, Michael S.; Hu, Doreen Autophagy, Vol. 5, Issue 6 https://doi.org/10.4161/auto.8824	journal	August 2009
Stationary phase in Saccharomyces cerevisiae Werner-Washburne, Margaret; Braun, Edward L.; Crawford, Matthew E. Molecular Microbiology, Vol. 19, Issue 6 https://doi.org/10.1111/j.1365-2958.1996.tb02461.x	journal	March 1996

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