Absence of mitochondrial translation control proteins extends life span by activating sirtuin-dependent silencing

Antonio Caballero; Ana Ugidos; Beidong Liu; David Öling; Kristian Kvint; Xinxin Hao; Cora Mignat; Laurence Nachin; Mikael Molin; Thomas Nyström

doi:10.1016/j.molcel.2011.03.021

Absence of mitochondrial translation control proteins extends life span by activating sirtuin-dependent silencing

Mol Cell. 2011 May 6;42(3):390-400. doi: 10.1016/j.molcel.2011.03.021.

Authors

Antonio Caballero¹, Ana Ugidos, Beidong Liu, David Öling, Kristian Kvint, Xinxin Hao, Cora Mignat, Laurence Nachin, Mikael Molin, Thomas Nyström

Affiliation

¹ Department of Cell and Molecular Biology, University of Gothenburg, Medicinaregatan 9C, 413 90 Göteborg, Sweden. antonio.caballero_reyes@kcl.ac.uk

PMID: 21549315
DOI: 10.1016/j.molcel.2011.03.021

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Blotting, Western
Cell Division / genetics
Cyclic AMP / metabolism
Cyclic AMP-Dependent Protein Kinases / metabolism
DNA-Binding Proteins
Gene Deletion
Gene Expression Profiling
Gene Expression Regulation, Fungal
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
Microscopy, Fluorescence
Mitochondrial Proteins / genetics*
Mitochondrial Proteins / metabolism
Mutation
Nicotinamidase / genetics
Nicotinamidase / metabolism
Oligonucleotide Array Sequence Analysis
Oxidative Stress
Reactive Oxygen Species / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Saccharomyces cerevisiae Proteins / genetics*
Saccharomyces cerevisiae Proteins / metabolism
Signal Transduction
Silent Information Regulator Proteins, Saccharomyces cerevisiae / genetics*
Silent Information Regulator Proteins, Saccharomyces cerevisiae / metabolism
Sirtuin 2 / genetics*
Sirtuin 2 / metabolism
Time Factors
Transcription Factors

Substances

DNA-Binding Proteins
MSN2 protein, S cerevisiae
MSN4 protein, S cerevisiae
Mitochondrial Proteins
Reactive Oxygen Species
SOV1 protein, S cerevisiae
Saccharomyces cerevisiae Proteins
Silent Information Regulator Proteins, Saccharomyces cerevisiae
Transcription Factors
Green Fluorescent Proteins
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
SIR2 protein, S cerevisiae
Sirtuin 2
Nicotinamidase
PNC1 protein, S cerevisiae