AMPK and vacuole-associated Atg14p orchestrate µ-lipophagy for energy production and long-term survival under glucose starvation
- Janelia Research Campus, Howard Hughes Medical Institute, United States
- National Institutes of Health, United States
- University of California, San Francisco, United States
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.
Article and author information
Author details
Jennifer Lippincott-Schwartz
Funding
Howard Hughes Medical Institute
- Jennifer Lippincott-Schwartz
National Institutes of Health
- Jennifer Lippincott-Schwartz
National Institute of General Medical Sciences (P41GM63948)
- Carolyn A Larabell
U.S. Department of Energy (DE-AC01-05CH11231)
- Carolyn A Larabell
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Vojo Deretic
Version history
- Received: September 20, 2016
- Accepted: April 9, 2017
- Accepted Manuscript published: April 10, 2017 (version 1)
- Version of Record published: April 27, 2017 (version 2)
Copyright
© 2017, Seo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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AMPK and vacuole-associated Atg14p orchestrate µ-lipophagy for energy production and long-term survival under glucose starvation
eLife 6:e21690.
https://doi.org/10.7554/eLife.21690
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