Compartment-specific perturbation of protein handling activates genes encoding mitochondrial chaperones

J Cell Sci. 2004 Aug 15;117(Pt 18):4055-66. doi: 10.1242/jcs.01275. Epub 2004 Jul 27.

Abstract

Protein folding in the mitochondria is assisted by nuclear-encoded compartment-specific chaperones but regulation of the expression of their encoding genes is poorly understood. We found that the mitochondrial matrix HSP70 and HSP60 chaperones, encoded by the Caenorhabditis elegans hsp-6 and hsp-60 genes, were selectively activated by perturbations that impair assembly of multi-subunit mitochondrial complexes or by RNAi of genes encoding mitochondrial chaperones or proteases, which lead to defective protein folding and processing in the organelle. hsp-6 and hsp-60 induction was specific to perturbed mitochondrial protein handling, as neither heat-shock nor endoplasmic reticulum stress nor manipulations that impair mitochondrial steps in intermediary metabolism or ATP synthesis activated the mitochondrial chaperone genes. These observations support the existence of a mitochondrial unfolded protein response that couples mitochondrial chaperone gene expression to changes in the protein handling environment in the organelle.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Cell Compartmentation / physiology*
  • Chaperonin 60 / chemistry
  • Chaperonin 60 / genetics*
  • Chaperonin 60 / metabolism
  • Endoplasmic Reticulum / metabolism
  • Energy Metabolism / physiology
  • Gene Expression Regulation / physiology
  • HSP70 Heat-Shock Proteins / chemistry
  • HSP70 Heat-Shock Proteins / genetics*
  • HSP70 Heat-Shock Proteins / metabolism
  • Heat-Shock Response / physiology
  • Intracellular Membranes / metabolism
  • Macromolecular Substances / metabolism
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / genetics*
  • Molecular Chaperones / metabolism
  • Oxidative Stress / physiology
  • Protein Folding
  • RNA Interference
  • Transcriptional Activation / physiology

Substances

  • Chaperonin 60
  • HSP70 Heat-Shock Proteins
  • Macromolecular Substances
  • Molecular Chaperones