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

Elife. 2019 Jan 15:8:e41792. doi: 10.7554/eLife.41792.

Abstract

Animals respond to mitochondrial stress with the induction of mitochondrial unfolded protein response (UPRmt). A cascade of events occur 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.

Keywords: C. elegans; cell biology; mitochondria; stress response; sumoylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / immunology*
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism*
  • Immunity, Innate*
  • Longevity / physiology*
  • Lysine / metabolism
  • Mitochondria / metabolism*
  • Models, Biological
  • Protein Stability
  • Signal Transduction
  • Sumoylation
  • Transcription, Genetic
  • Unfolded Protein Response*

Substances

  • Caenorhabditis elegans Proteins
  • Cysteine Endopeptidases
  • ULP-4 protein, C elegans
  • Lysine