title: In mammalian muscle, SIRT3 is present in mitochondria and not in the nucleus; and SIRT3 is upregulated by chronic muscle contraction in an adenosine monophosphate-activated protein kinase-independent manner.
abstract: In selected cell lines, it appears (a) that metabolic stressors induce the translocation of SIRT3 from the nucleus to mitochondria and (b) that SIRT3 may contribute to the regulation of mitochondrial biogenesis and/or fatty acid utilization. We have examined in mammalian muscle (1) the association between SIRT3 protein content and muscle oxidative capacity and mitochondrial fatty acid oxidation, (2) the subcellular location of SIRT3, (3) whether exercise induces the translocation of SIRT3 from the nucleus to the mitochondria, and (4) the response of SIRT3 protein to stressors known to induce mitochondrial biogenesis (chronic muscle stimulation and 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside administration). SIRT3 protein displayed hierarchical expression based on oxidative potential of muscle tissues (heart >> red >> white). In contrast to studies in some cell lines, metabolic stress (exercise) did not induce the translocation of SIRT3 from the nucleus to mitochondria, as SIRT3 was only present in subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria, not in the nucleus. Chronic stimulation increased muscle mitochondrial content and SIRT3 protein in SS (+33%) and IMF (+27%) mitochondria (P < .05). In contrast, chronic 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside administration, while inducing mitochondrial biogenesis, did not alter SS or IMF mitochondrial SIRT3 protein content. These studies have shown that, in muscle, SIRT3 (a) scales with muscle oxidative capacity and with enzymes regulating fatty acid oxidation, (b) in resting muscle is localized to SS and IMF mitochondria and not nuclei, (c) in contracting muscle is not acutely translocated to mitochondria, and (d) is upregulated with chronic stimulation in an adenosine monophosphate-activated protein kinase-independent manner.
authors.affiliation: School of Kinesiology, Queen's University, Kingston, Ontario, Canada K7L 3N6. gurdb@queensu.ca
authors.forename: Brendon J
authors.initials: BJ
authors.lastname: Gurd
authors.forename: Graham P
authors.initials: GP
authors.lastname: Holloway
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Arend
authors.initials: A
authors.lastname: Bonen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004558:Electric Stimulation; D004746:Enoyl-CoA Hydratase / Q000378:metabolism; D005260:Female; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology*; D019308:Palmitic Acid / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012265:Ribonucleotides / Q000494:pharmacology; D056564:Sirtuin 1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D012265:Ribonucleotides; D014157:Transcription Factors; D019308:Palmitic Acid; D000620:Aminoimidazole Carboxamide; D002334:Carnitine O-Palmitoyltransferase; D002950:Citrate (si)-Synthase; D055372:AMP-Activated Protein Kinases; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D004746:Enoyl-CoA Hydratase; C031143:AICA ribonucleotide