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

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Abstract

Animals respond to mitochondrial stress with the induction of mitochondrial unfolded protein response (UPR^mt). A cascade of events occurs upon UPR^mt 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 UPR^mt to control SUMOylation status of DVE-1 and ATFS-1. SUMOylation affects these two axes in the transcriptional program of UPR^mt 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.

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

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Kaiyu Gao

Institute of Molecular Medicine, Peking University, Beijing, China

Competing interests
The authors declare that no competing interests exist.
Yi Li

Institute of Molecular Medicine, Peking University, Beijing, China

Competing interests
The authors declare that no competing interests exist.
Shumei Hu

Institute of Molecular Medicine, Peking University, Beijing, China

Competing interests
The authors declare that no competing interests exist.
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.

"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.

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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.