title: The role of nNOS and PGC-1α in skeletal muscle cells.
abstract: Neuronal nitric oxide synthase (nNOS) and peroxisome proliferator activated receptor γ co-activator 1α (PGC-1α) are two fundamental factors involved in the regulation of skeletal muscle cell metabolism. nNOS exists as several alternatively spliced variants, each having a specific pattern of subcellular localisation. Nitric oxide (NO) functions as a second messenger in signal transduction pathways that lead to the expression of metabolic genes involved in oxidative metabolism, vasodilatation and skeletal muscle contraction. PGC-1α is a transcriptional coactivator and represents a master regulator of mitochondrial biogenesis by promoting the transcription of mitochondrial genes. PGC-1α can be induced during physical exercise, and it plays a key role in coordinating the oxidation of intracellular fatty acids with mitochondrial remodelling. Several lines of evidence demonstrate that NO could act as a key regulator of PGC-1α expression; however, the link between nNOS and PGC-1α in skeletal muscle remains only poorly understood. In this Commentary, we review important metabolic pathways that are governed by nNOS and PGC-1α, and aim to highlight how they might intersect and cooperatively regulate skeletal muscle mitochondrial and lipid energetic metabolism and contraction.
authors.affiliation: Scientific Institute for Research, Hospitalization and Health Care, Università Telematica San Raffaele Roma, Via di Val Cannuta, 00167, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Baldelli
authors.affiliation: Department of Biology, University of Rome 'Tor Vergata', Via della Ricerca Scientifica, 00133 Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Lettieri Barbato
authors.affiliation: Scientific Institute for Research, Hospitalization and Health Care, Università Telematica San Raffaele Roma, Via di Val Cannuta, 00167, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tatulli
authors.affiliation: Department of Biology, University of Rome 'Tor Vergata', Via della Ricerca Scientifica, 00133 Rome, Italy katia.aquilano@uniroma2.it ciriolo@bio.uniroma2.it.
authors.forename: Katia
authors.initials: K
authors.lastname: Aquilano
authors.affiliation: IRCCS San Raffaele 'La Pisana', Via di Val Cannuta, 00166, Rome, Italy katia.aquilano@uniroma2.it ciriolo@bio.uniroma2.it.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Ciriolo
mesh_terms: D000818:Animals; D006801:Humans; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011994:Recombinant Proteins; D014157:Transcription Factors; C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I
keywords: Lipid metabolism; Mitochondrial biogenesis; Mitochondrial metabolism; Nitric oxide