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

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eLife. 2017 Apr 10;6:e21690. doi: 10.7554/eLife.21690
AMPK and vacuole-associated Atg14p orchestrate µ-lipophagy for energy production and long-term survival under glucose starvation. Lippincott-Schwartz LabFeliciano Lab
Seo AY, Lau P, Feliciano D, Sengupta P, Le Gros MA, Cinquin B, Larabell CA, Lippincott-Schwartz J
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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.

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Janelia Authors

Daniel Feliciano
Prabuddha Sengupta
Jennifer Lippincott-Schwartz
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