| A novel AMPK-dependent FoxO3A-SIRT3 intramitochondrial complex sensing glucose levels. | |
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MedLine Citation:
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PMID: 23283301 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2013-1-3 |
Journal Detail:
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Title: Cellular and molecular life sciences : CMLS Volume: - ISSN: 1420-9071 ISO Abbreviation: Cell. Mol. Life Sci. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9705402 Medline TA: Cell Mol Life Sci Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Laboratory of Signal-dependent Transcription, Department of Translational Pharmacology (DTP), Consorzio Mario Negri Sud, 66030, Santa Maria Imbaro (Ch), Italy. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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