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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.

Author information

1
Scientific Institute for Research, Hospitalization and Health Care, Università Telematica San Raffaele Roma, Via di Val Cannuta, 00167, Rome, Italy.
2
Department of Biology, University of Rome 'Tor Vergata', Via della Ricerca Scientifica, 00133 Rome, Italy.
3
Department of Biology, University of Rome 'Tor Vergata', Via della Ricerca Scientifica, 00133 Rome, Italy katia.aquilano@uniroma2.it ciriolo@bio.uniroma2.it.
4
IRCCS San Raffaele 'La Pisana', Via di Val Cannuta, 00166, Rome, Italy katia.aquilano@uniroma2.it ciriolo@bio.uniroma2.it.

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.

KEYWORDS:

Lipid metabolism; Mitochondrial biogenesis; Mitochondrial metabolism; Nitric oxide

PMID:
25217629
DOI:
10.1242/jcs.154229
[Indexed for MEDLINE]
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