The mitochondrial unfolded protein response and increased longevity: cause, consequence, or correlation?

Exp Gerontol. 2014 Aug;56:142-6. doi: 10.1016/j.exger.2014.02.002. Epub 2014 Feb 8.

Abstract

The mitochondrial unfolded protein response is a conserved pathway that allows mitochondrial chaperones and other factors to be induced in response to mitochondrial dysfunction. Activation of this pathway has been proposed to underlie lifespan extension from knockdown or mutation of several nuclear encoded mitochondrial genes in Caenorhabditis elegans. In some cases, however, induction of the mitochondrial unfolded protein response is associated with a reduction of lifespan in both yeast and C. elegans. It also has yet to be demonstrated that induction of the mitochondrial unfolded protein response is sufficient to increase lifespan in the absence of overt mitochondrial dysfunction. In this perspective, we briefly review the evidence for and against a direct pro-longevity role of the mitochondrial unfolded protein response and suggest important areas of investigation for experimentally addressing this question.

Keywords: ATFS-1; C. elegans; HSP-6; Mitochondrial unfolded protein response; Prohibitins.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Age Factors
  • Aging / metabolism*
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Humans
  • Longevity*
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Models, Animal
  • Signal Transduction
  • Unfolded Protein Response*

Substances

  • Caenorhabditis elegans Proteins
  • Mitochondrial Proteins