title: UPR(mt)-mediated cytoprotection and organismal aging.
abstract: Time- or age-dependent accumulation of mitochondrial damage and dysfunction is strongly associated with aging [1]. Thus, a major biomedical goal is to identify and therapeutically manipulate those inherent programs that protect against mitochondrial dysfunction to promote cell survival and organismal health. The mitochondrial unfolded protein response (UPR(mt)) is such a protective transcriptional response mediated by mitochondrial-to-nuclear signaling that includes mitochondrial proteostasis genes to stabilize mitochondrial function, metabolic adaptations, as well as an innate immunity program. Here, we review the UPR(mt) and its role during a variety of forms of mitochondrial dysfunction including those caused by mutations in respiratory chain genes as well as upon exposure to pathogens that produce mitochondrial toxins. We also review recent data in support of and against the emerging role of the UPR(mt) during aging and longevity. This article is part of a Special Issue entitled: Mitochondrial Dysfunction in Aging.
authors: Cell Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: schulza@mskcc.org.
authors: Anna M
authors: AM
authors: Schulz
authors: Cell Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; BCMB Allied Program, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA. Electronic address: haynesc@mskcc.org.
authors: Cole M
authors: CM
authors: Haynes
mesh_terms: D000375:Aging; D000818:Animals; D019610:Cytoprotection; D006801:Humans; D007113:Immunity, Innate; D008928:Mitochondria / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D056811:Unfolded Protein Response
chemical_list: C529271:EIF2AK4 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: ATFS-1; Innate immunity; Metabolism; Mitochondrial dysfunction; Mitochondrial unfolded protein response