Mitochondrial Stress Induces Chromatin Reorganization to Promote Longevity and UPR(mt)

Cell. 2016 May 19;165(5):1197-1208. doi: 10.1016/j.cell.2016.04.011. Epub 2016 Apr 28.

Abstract

Organisms respond to mitochondrial stress through the upregulation of an array of protective genes, often perpetuating an early response to metabolic dysfunction across a lifetime. We find that mitochondrial stress causes widespread changes in chromatin structure through histone H3K9 di-methylation marks traditionally associated with gene silencing. Mitochondrial stress response activation requires the di-methylation of histone H3K9 through the activity of the histone methyltransferase met-2 and the nuclear co-factor lin-65. While globally the chromatin becomes silenced by these marks, remaining portions of the chromatin open up, at which point the binding of canonical stress responsive factors such as DVE-1 occurs. Thus, a metabolic stress response is established and propagated into adulthood of animals through specific epigenetic modifications that allow for selective gene expression and lifespan extension.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / metabolism
  • Chromatin Assembly and Disassembly*
  • Epigenesis, Genetic
  • Gene Expression Regulation
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histones / metabolism
  • Longevity
  • Mitochondria / metabolism
  • Unfolded Protein Response*

Substances

  • Caenorhabditis elegans Proteins
  • Histones
  • Histone-Lysine N-Methyltransferase
  • Met-2 protein, C elegans