1. Cell Biology

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

  1. Arnold Young Seo
  2. Pick-Wei Lau
  3. Daniel Feliciano
  4. Prabuddha Sengupta
  5. Mark A Le Gros
  6. Bertrand Cinquin
  7. Carolyn A Larabell
  8. Jennifer Lippincott-Schwartz  Is a corresponding author
  1. Janelia Research Campus, Howard Hughes Medical Institute, United States
  2. National Institutes of Health, United States
  3. University of California, San Francisco, United States
https://doi.org/10.7554/eLife.21690
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Cite this article
  1. Arnold Young Seo
  2. Pick-Wei Lau
  3. Daniel Feliciano
  4. Prabuddha Sengupta
  5. Mark A Le Gros
  6. Bertrand Cinquin
  7. Carolyn A Larabell
  8. Jennifer Lippincott-Schwartz
(2017)
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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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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Author details

  1. Arnold Young Seo

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Pick-Wei Lau

    Cell Biology and Metabolism Program, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Daniel Feliciano

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Prabuddha Sengupta

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Mark A Le Gros

    Department of Anatomy, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Bertrand Cinquin

    Department of Anatomy, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Carolyn A Larabell

    Department of Anatomy, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Jennifer Lippincott-Schwartz

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    For correspondence
    lippincottschwartzj@janelia.hhmi.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8601-3501

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.

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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  1. Arnold Young Seo
  2. Pick-Wei Lau
  3. Daniel Feliciano
  4. Prabuddha Sengupta
  5. Mark A Le Gros
  6. Bertrand Cinquin
  7. Carolyn A Larabell
  8. Jennifer Lippincott-Schwartz
(2017)
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

Share this article

https://doi.org/10.7554/eLife.21690

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