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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:
ORCiD logo [1];  [2];  [1];  [1];  [3];  [4]; ORCiD logo [3]; ORCiD logo [1]
  1. Howard Hughes Medical Institute, Ashburn, VA (United States); National Institutes of Health, Bethesda, MD (United States)
  2. National Institutes of Health, Bethesda, MD (United States)
  3. Univ. of California, San Francisco, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  4. Univ. of California, San Francisco, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1351057
Alternate Identifier(s):
OSTI ID: 1351058; OSTI ID: 1379802
Grant/Contract Number:  
AC02-05CH11231; AC02-5CH11231
Resource Type:
Journal Article: Published Article
Journal Name:
eLife
Additional Journal Information:
Journal Volume: 6; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Seo, Arnold Y., Lau, Pick -Wei, Feliciano, Daniel, Sengupta, Prabuddha, Gros, Mark A. Le, Cinquin, Bertrand, Larabell, Carolyn A., and Lippincott-Schwartz, Jennifer. AMPK and vacuole-associated Atg14p orchestrate μ-lipophagy for energy production and long-term survival under glucose starvation. United States: N. p., 2017. Web. doi:10.7554/eLife.21690.
Seo, Arnold Y., Lau, Pick -Wei, Feliciano, Daniel, Sengupta, Prabuddha, Gros, Mark A. Le, Cinquin, Bertrand, Larabell, Carolyn A., & Lippincott-Schwartz, Jennifer. AMPK and vacuole-associated Atg14p orchestrate μ-lipophagy for energy production and long-term survival under glucose starvation. United States. doi:10.7554/eLife.21690.
Seo, Arnold Y., Lau, Pick -Wei, Feliciano, Daniel, Sengupta, Prabuddha, Gros, Mark A. Le, Cinquin, Bertrand, Larabell, Carolyn A., and Lippincott-Schwartz, Jennifer. Mon . "AMPK and vacuole-associated Atg14p orchestrate μ-lipophagy for energy production and long-term survival under glucose starvation". United States. doi:10.7554/eLife.21690.
@article{osti_1351057,
title = {AMPK and vacuole-associated Atg14p orchestrate μ-lipophagy for energy production and long-term survival under glucose starvation},
author = {Seo, Arnold Y. and Lau, Pick -Wei and Feliciano, Daniel and Sengupta, Prabuddha and Gros, Mark A. Le and Cinquin, Bertrand and Larabell, Carolyn A. and Lippincott-Schwartz, Jennifer},
abstractNote = {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.},
doi = {10.7554/eLife.21690},
journal = {eLife},
number = ,
volume = 6,
place = {United States},
year = {Mon Apr 10 00:00:00 EDT 2017},
month = {Mon Apr 10 00:00:00 EDT 2017}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.7554/eLife.21690

Citation Metrics:
Cited by: 15 works
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Works referenced in this record:

Good Fat, Essential Cellular Requirements for Triacylglycerol Synthesis to Maintain Membrane Homeostasis in Yeast
journal, July 2009

  • Petschnigg, Julia; Wolinski, Heimo; Kolb, Dagmar
  • Journal of Biological Chemistry, Vol. 284, Issue 45, p. 30981-30993
  • DOI: 10.1074/jbc.M109.024752