Baldelli Sara, Lettieri Barbato Daniele, Tatulli Giuseppe, Aquilano Katia, Ciriolo Maria Rosa
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.
J Cell Sci. 2014 Nov 15;127(Pt 22):4813-20. doi: 10.1242/jcs.154229. Epub 2014 Sep 12.
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.
神经元型一氧化氮合酶（nNOS）和过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）是参与骨骼肌细胞代谢调节的两个基本因子。nNOS以几种可变剪接变体的形式存在，每种变体都有特定的亚细胞定位模式。一氧化氮（NO）在信号转导途径中作为第二信使，这些途径导致参与氧化代谢、血管舒张和骨骼肌收缩的代谢基因的表达。PGC-1α是一种转录共激活因子，通过促进线粒体基因的转录，代表线粒体生物发生的主要调节因子。PGC-1α可在体育锻炼过程中被诱导，并且在协调细胞内脂肪酸氧化与线粒体重塑方面发挥关键作用。多项证据表明，NO可能是PGC-1α表达的关键调节因子；然而，骨骼肌中nNOS与PGC-1α之间的联系仍知之甚少。在本述评中，我们综述了由nNOS和PGC-1α调控的重要代谢途径，旨在强调它们可能如何相互交叉并协同调节骨骼肌线粒体和脂质能量代谢以及收缩。
