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

Sara Baldelli, Daniele Lettieri Barbato, Giuseppe Tatulli, Katia Aquilano, Maria Rosa Ciriolo

Research output: Contribution to journalArticle


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.

Original languageEnglish
Pages (from-to)4813-4820
Number of pages8
JournalJournal of Cell Science
Issue number22
Publication statusPublished - 2014


  • Lipid metabolism
  • Mitochondrial biogenesis
  • Mitochondrial metabolism
  • Nitric oxide

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

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