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J Cell Sci. 2014 Nov 15;127(Pt 22):4813-20. doi: 10.1242/jcs.154229. Epub 2014 Sep 12.

The role of nNOS and PGC-1α in skeletal muscle cells.

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Scientific Institute for Research, Hospitalization and Health Care, Università Telematica San Raffaele Roma, Via di Val Cannuta, 00167, Rome, Italy.
Department of Biology, University of Rome 'Tor Vergata', Via della Ricerca Scientifica, 00133 Rome, Italy.
Department of Biology, University of Rome 'Tor Vergata', Via della Ricerca Scientifica, 00133 Rome, Italy
IRCCS San Raffaele 'La Pisana', Via di Val Cannuta, 00166, Rome, Italy


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.


Lipid metabolism; Mitochondrial biogenesis; Mitochondrial metabolism; Nitric oxide

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