SUMO peptidase ULP-4 regulates mitochondrial UPR-mediated innate immunity and lifespan extension
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
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
- Hong Zhang, Institute of Biophysics, Chinese Academy of Sciences, China
Version history
- Received: September 6, 2018
- Accepted: January 2, 2019
- Accepted Manuscript published: January 15, 2019 (version 1)
- 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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