title: Activation of the mitochondrial unfolded protein response does not predict longevity in Caenorhabditis elegans.
abstract: Recent studies have propagated the model that the mitochondrial unfolded protein response (UPR(mt)) is causal for lifespan extension from inhibition of the electron transport chain (ETC) in Caenorhabditis elegans. Here we report a genome-wide RNAi screen for negative regulators of the UPR(mt). Lifespan analysis of nineteen RNAi clones that induce the hsp-6p::gfp reporter demonstrate differential effects on longevity. Deletion of atfs-1, which is required for induction of the UPR(mt), fails to prevent lifespan extension from knockdown of two genes identified in our screen or following knockdown of the ETC gene cco-1. RNAi knockdown of atfs-1 also has no effect on lifespan extension caused by mutation of the ETC gene isp-1. Constitutive activation of the UPR(mt) by gain of function mutations in atfs-1 fails to extend lifespan. These observations identify several new factors that promote mitochondrial homoeostasis and demonstrate that the UPR(mt), as currently defined, is neither necessary nor sufficient for lifespan extension.
authors.affiliation: 1] Department of Pathology, University of Washington, 1959 NE Pacific Street, D-514, Box 357470, Seattle, Washington 98195-7470, USA [2] Molecular and Cellular Biology Program, University of Washington, 1959 NE Pacific Street, Seattle, Washington 98195-7470, USA.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Bennett
authors.affiliation: Department of Pathology, University of Washington, 1959 NE Pacific Street, D-514, Box 357470, Seattle, Washington 98195-7470, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Vander Wende
authors.affiliation: Department of Pathology, University of Washington, 1959 NE Pacific Street, D-514, Box 357470, Seattle, Washington 98195-7470, USA.
authors.forename: Marissa
authors.initials: M
authors.lastname: Simko
authors.affiliation: Department of Pathology, University of Washington, 1959 NE Pacific Street, D-514, Box 357470, Seattle, Washington 98195-7470, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Klum
authors.affiliation: Department of Pathology, University of Washington, 1959 NE Pacific Street, D-514, Box 357470, Seattle, Washington 98195-7470, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Barfield
authors.affiliation: Department of Pathology, University of Washington, 1959 NE Pacific Street, D-514, Box 357470, Seattle, Washington 98195-7470, USA.
authors.forename: Haeri
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Pathology, University of Washington, 1959 NE Pacific Street, D-514, Box 357470, Seattle, Washington 98195-7470, USA.
authors.forename: Victor V
authors.initials: VV
authors.lastname: Pineda
authors.affiliation: Department of Pathology, University of Washington, 1959 NE Pacific Street, D-514, Box 357470, Seattle, Washington 98195-7470, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Kaeberlein
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins; D008136:Longevity / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism*; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D056811:Unfolded Protein Response / Q000502:physiology*
chemical_list: C548052:ATFS-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins