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A novel AMPK-dependent FoxO3A-SIRT3 intramitochondrial complex sensing glucose levels.
MedLine Citation:
PMID:  23283301     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Reduction of nutrient intake without malnutrition positively influences lifespan and healthspan from yeast to mice and exerts some beneficial effects also in humans. The AMPK-FoxO axis is one of the evolutionarily conserved nutrient-sensing pathways, and the FOXO3A locus is associated with human longevity. Interestingly, FoxO3A has been reported to be also a mitochondrial protein in mammalian cells and tissues. Here we report that glucose restriction triggers FoxO3A accumulation into mitochondria of fibroblasts and skeletal myotubes in an AMPK-dependent manner. A low-glucose regimen induces the formation of a protein complex containing FoxO3A, SIRT3, and mitochondrial RNA polymerase (mtRNAPol) at mitochondrial DNA-regulatory regions causing activation of the mitochondrial genome and a subsequent increase in mitochondrial respiration. Consistently, mitochondrial transcription increases in skeletal muscle of fasted mice, with a mitochondrial DNA-bound FoxO3A/SIRT3/mtRNAPol complex detectable also in vivo. Our results unveil a mitochondrial arm of the AMPK-FoxO3A axis acting as a recovery mechanism to sustain energy metabolism upon nutrient restriction.
Authors:
Alessia Peserico; Fulvio Chiacchiera; Valentina Grossi; Antonio Matrone; Dominga Latorre; Marta Simonatto; Aurora Fusella; James G Ryall; Lydia W S Finley; Marcia C Haigis; Gaetano Villani; Pier Lorenzo Puri; Vittorio Sartorelli; Cristiano Simone
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-3
Journal Detail:
Title:  Cellular and molecular life sciences : CMLS     Volume:  -     ISSN:  1420-9071     ISO Abbreviation:  Cell. Mol. Life Sci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9705402     Medline TA:  Cell Mol Life Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratory of Signal-dependent Transcription, Department of Translational Pharmacology (DTP), Consorzio Mario Negri Sud, 66030, Santa Maria Imbaro (Ch), Italy.
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