SUMO peptidase ULP-4 regulates mitochondrial UPR-mediated innate immunity and lifespan extension

  1. Kaiyu Gao
  2. Yi Li
  3. Shumei Hu
  4. Ying Liu  Is a corresponding author
  1. Peking University, China

Abstract

Animals respond to mitochondrial stress with the induction of mitochondrial unfolded protein response (UPRmt). A cascade of events occurs upon UPRmt activation, ultimately triggering a transcriptional response governed by two transcription factors: DVE-1 and ATFS-1. Here we identify SUMO-specific peptidase ULP-4 as a positive regulator of C. elegans UPRmt to control SUMOylation status of DVE-1 and ATFS-1. SUMOylation affects these two axes in the transcriptional program of UPRmt with distinct mechanisms: change of DVE-1 subcellular localization vs. change of ATFS-1 stability and activity. Our findings reveal a post-translational modification that promotes immune response and lifespan extension during mitochondrial stress.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Kaiyu Gao

    Institute of Molecular Medicine, Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Yi Li

    Institute of Molecular Medicine, Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Shumei Hu

    Institute of Molecular Medicine, Peking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Ying Liu

    Institute of Molecular Medicine, Peking University, Beijing, China
    For correspondence
    ying.liu@pku.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3328-026X

Funding

National Natural Science Foundation of China (91854205)

  • Ying Liu

Ministry of Science and Technology of the People's Republic of China (2017YFA0504000973)

  • Ying Liu

Howard Hughes Medical Institute (55008739)

  • Ying Liu

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

Reviewing Editor

  1. Hong Zhang, Institute of Biophysics, Chinese Academy of Sciences, China

Publication history

  1. Received: September 6, 2018
  2. Accepted: January 2, 2019
  3. Accepted Manuscript published: January 15, 2019 (version 1)
  4. Version of Record published: January 31, 2019 (version 2)

Copyright

© 2019, Gao 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. Kaiyu Gao
  2. Yi Li
  3. Shumei Hu
  4. Ying Liu
(2019)
SUMO peptidase ULP-4 regulates mitochondrial UPR-mediated innate immunity and lifespan extension
eLife 8:e41792.
https://doi.org/10.7554/eLife.41792

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