title: The mitochondrial unfolded protein response and increased longevity: cause, consequence, or correlation?
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.
authors: Department of Pathology, University of Washington, Seattle, WA, USA; Molecular and Cellular Biology Program, University of Washington, Seattle, WA, USA.
authors: Christopher F
authors: CF
authors: Bennett
authors: Department of Pathology, University of Washington, Seattle, WA, USA. Electronic address: kaeber@uw.edu.
authors: Matt
authors: M
authors: Kaeberlein
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008136:Longevity; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D023421:Models, Animal; D015398:Signal Transduction; D056811:Unfolded Protein Response
chemical_list: D029742:Caenorhabditis elegans Proteins; D024101:Mitochondrial Proteins
keywords: ATFS-1; C. elegans; HSP-6; Mitochondrial unfolded protein response; Prohibitins