title: Absence of mitochondrial translation control proteins extends life span by activating sirtuin-dependent silencing.
abstract: Altered mitochondrial functionality can extend organism life span, but the underlying mechanisms are obscure. Here we report that inactivating SOV1, a member of the yeast mitochondrial translation control (MTC) module, causes a robust Sir2-dependent extension of replicative life span in the absence of respiration and without affecting oxidative damage. We found that SOV1 interacts genetically with the cAMP-PKA pathway and the chromatin remodeling apparatus. Consistently, Sov1p-deficient cells displayed reduced cAMP-PKA signaling and an elevated, Sir2p-dependent, genomic silencing. Both increased silencing and life span extension in sov1Δ cells require the PKA/Msn2/4p target Pnc1p, which scavenges nicotinamide, a Sir2p inhibitor. Inactivating other members of the MTC module also resulted in Sir2p-dependent life span extension. The data demonstrate that the nuclear silencing apparatus senses and responds to the absence of MTC proteins and that this response converges with a pathway for life span extension elicited by reducing TOR signaling.
authors.affiliation: Department of Cell and Molecular Biology, University of Gothenburg, Medicinaregatan 9C, 413 90 Göteborg, Sweden. antonio.caballero_reyes@kcl.ac.uk
authors.forename: Antonio
authors.initials: A
authors.lastname: Caballero
authors.forename: Ana
authors.initials: A
authors.lastname: Ugidos
authors.forename: Beidong
authors.initials: B
authors.lastname: Liu
authors.forename: David
authors.initials: D
authors.lastname: Öling
authors.forename: Kristian
authors.initials: K
authors.lastname: Kvint
authors.forename: Xinxin
authors.initials: X
authors.lastname: Hao
authors.forename: Cora
authors.initials: C
authors.lastname: Mignat
authors.forename: Laurence
authors.initials: L
authors.lastname: Nachin
authors.forename: Mikael
authors.initials: M
authors.lastname: Molin
authors.forename: Thomas
authors.initials: T
authors.lastname: Nyström
mesh_terms: D015153:Blotting, Western; D002455:Cell Division / Q000235:genetics; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009535:Nicotinamidase / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D056565:Sirtuin 2 / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; C081935:MSN2 protein, S cerevisiae; C081937:MSN4 protein, S cerevisiae; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C559858:SOV1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D009535:Nicotinamidase; C474330:PNC1 protein, S cerevisiae