1. Cell Biology
  2. Chromosomes and Gene Expression

PGAM5 promotes lasting FoxO activation after developmental mitochondrial stress and extends lifespan in Drosophila

  1. Martin Borch Jensen  Is a corresponding author
  2. Yanyan Qi
  3. Rebeccah Riley
  4. Liya Rabkina
  5. Heinrich Jasper  Is a corresponding author
  1. Buck Institute for Research on Aging, United States
  2. Buck Institute For Research On Aging, United States
https://doi.org/10.7554/eLife.26952
Share this article
Cite this article
  1. Martin Borch Jensen
  2. Yanyan Qi
  3. Rebeccah Riley
  4. Liya Rabkina
  5. Heinrich Jasper
(2017)
PGAM5 promotes lasting FoxO activation after developmental mitochondrial stress and extends lifespan in Drosophila
eLife 6:e26952.
https://doi.org/10.7554/eLife.26952
  2. Download BibTeX
  3. Download .RIS

Abstract

The mitochondrial unfolded protein response (UPRmt) has been associated with long lifespan across metazoans. In C. elegans, mild developmental mitochondrial stress activates UPRmt reporters and extends lifespan. We show that similar developmental stress is necessary and sufficient to extend Drosophila lifespan, and identify Phosphoglycerate Mutase 5 (PGAM5) as a mediator of this response. Developmental mitochondrial stress leads to activation of FoxO, via Apoptosis Signal-regulating Kinase 1 (ASK1) and Jun-N-terminal Kinase (JNK). This activation persists into adulthood and induces a select set of chaperones, many of which have been implicated in lifespan extension in flies. Persistent FoxO activation can be reversed by a high protein diet in adulthood, through mTORC1 and GCN-2 activity. Accordingly, the observed lifespan extension is prevented on a high protein diet and in FoxO-null flies. The diet-sensitivity of this pathway has important implications for interventions that seek to engage the UPRmt to improve metabolic health and longevity.

Article and author information

Author details

  1. Martin Borch Jensen

    Buck Institute for Research on Aging, Novato, United States
    For correspondence
    martinborchjensen@gmail.com
    Competing interests
    The authors declare that no competing interests exist.

  2. Yanyan Qi

    Buck Institute for Research on Aging, Novato, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Rebeccah Riley

    Buck Institute for Research on Aging, Novato, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Liya Rabkina

    Buck Institute for Research on Aging, Novato, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Heinrich Jasper

    Buck Institute For Research On Aging, Novato, United States
    For correspondence
    hjasper@buckinstitute.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6014-4343

Funding

National Institute on Aging (R01 AG028127)

  • Yanyan Qi
  • Rebeccah Riley
  • Heinrich Jasper

American Federation for Aging Research (Breakthroughs in Gerontology award)

  • Heinrich Jasper

Alfred Benzon Foundation (Postdoctoral fellowship)

  • Martin Borch Jensen

National Institute on Aging (R01 AG050104)

  • Yanyan Qi
  • Rebeccah Riley
  • Heinrich Jasper

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2017, Borch Jensen 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.

Metrics

  • 3,417
    views
  • 746
    downloads
  • 46
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Martin Borch Jensen
  2. Yanyan Qi
  3. Rebeccah Riley
  4. Liya Rabkina
  5. Heinrich Jasper
(2017)
PGAM5 promotes lasting FoxO activation after developmental mitochondrial stress and extends lifespan in Drosophila
eLife 6:e26952.
https://doi.org/10.7554/eLife.26952

Share this article

https://doi.org/10.7554/eLife.26952

Categories and tags

Research organism

Further reading

    1. Cell Biology

    Distinct trafficking routes of polarized and non-polarized membrane cargoes in Aspergillus nidulans

    Georgia Maria Sagia, Xenia Georgiou ... Sofia Dimou
    Research Article Updated

    Membrane proteins are sorted to the plasma membrane via Golgi-dependent trafficking. However, our recent studies challenged the essentiality of Golgi in the biogenesis of specific transporters. Here, we investigate the trafficking mechanisms of membrane proteins by following the localization of the polarized R-SNARE SynA versus the non-polarized transporter UapA, synchronously co-expressed in wild-type or isogenic genetic backgrounds repressible for conventional cargo secretion. In wild-type, the two cargoes dynamically label distinct secretory compartments, highlighted by the finding that, unlike SynA, UapA does not colocalize with the late-Golgi. In line with early partitioning into distinct secretory carriers, the two cargoes collapse in distinct ER-Exit Sites (ERES) in a sec31ts background. Trafficking via distinct cargo-specific carriers is further supported by showing that repression of proteins essential for conventional cargo secretion does not affect UapA trafficking, while blocking SynA secretion. Overall, this work establishes the existence of distinct, cargo-dependent, trafficking mechanisms, initiating at ERES and being differentially dependent on Golgi and SNARE interactions.

    1. Cell Biology

    Microbiome: Balancing microbial composition through diet

    L Catalina Acuff, Karen Guillemin
    Insight

    A reciprocal interaction between gut bacteria and gut cells affects protein absorption in the host.