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

Gao, Kaiyu; Li, Yi; Hu, Shumei; Liu, Ying · Elife · 2019

basic_science · Level V

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Abstract

Animals respond to mitochondrial stress with the induction of mitochondrial unfolded protein response (UPR<sup>mt</sup>). A cascade of events occur upon UPR<sup>mt</sup> 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 <i>C. elegans</i> UPR<sup>mt</sup> to control SUMOylation status of DVE-1 and ATFS-1. SUMOylation affects these two axes in the transcriptional program of UPR<sup>mt</sup> 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.

Medical subject headings