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

• Published in: eLife Vol. 8
• Main Authors: Gao, Kaiyu, Li, Yi, Hu, Shumei, Liu, Ying
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 15.01.2019; eLife Sciences Publications, Ltd
• Subjects: Animals; Caenorhabditis elegans - genetics; Caenorhabditis elegans - immunology; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell Biology; Chromatin; CRISPR; Enzymes; Genes; Homeostasis; Immune response; Immunity, Innate; Innate immunity; Laboratories; Life span; Localization; Longevity - physiology; Lysine - metabolism; Medical research; Metabolism; Mitochondria; Mitochondria - metabolism; Models, Biological; Peptidase; Post-translation; Protein folding; Protein Stability; Proteins; Signal Transduction; Statistical analysis; Stress response; SUMO protein; Sumoylation; Transcription activation; Transcription factors; Transcription, Genetic; Unfolded Protein Response; Beijing China; C. elegans; cell biology; stress response; sumoylation; mitochondria
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/ELIFE.41792

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