The role of autophagy and lysosomal degradation pathway in the regulation of skeletal muscle metabolism was previously studied. However, underlying molecular mechanisms are poorly understood. L-lactate which is utilized as an energetic substrate by skeletal muscle can also augment genes expression related to metabolism and up-regulate those being responsive to reactive oxygen species (ROS). Since ROS is the most important regulator of autophagy in skeletal muscle, we tested if there is a link between cellular lactate metabolism and autophagy in differentiated C2C12 myotubes and the gastrocnemius muscle of male wistar rats. C2C12 mouse skeletal muscle was exposed to 2, 6, 10, and 20 mM lactate and evaluated for lactate autophagic effects. Lactate dose-dependently increased autophagy and augmented ROS generation in differentiated C2C12 myotubes. The autophagic effect of lactate deterred in N-acetylcysteine presence (NAC, a ROS scavenger) indicated lactate regulates autophagy with ROS participation. Lactate-induced up-regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) through ROS was required to regulate the autophagy by lactate. Further analysis about ERK1/2 up- and downstream indicated that lactate regulates autophagy through ROS-mediated the activation of ERK1/2/mTOR/p70S6K pathway in skeletal muscle. The in vitro effects of lactate on autophagy also occurred in the gastrocnemius muscle of male Wistar rats. In conclusion, we provided the lactate-associated regulation evidence of autophagy in skeletal muscle by activating ROS-mediated ERK1/2/mTOR/p70S6K pathway. Since the increase in cellular lactate concentration is a hallmark of energy deficiency, the results provide insight into a skeletal muscle mechanism to fulfill its enhanced energy requirement.

以前已经研究了自噬和溶酶体降解途径在调节骨骼肌代谢中的作用。然而，人们对潜在的分子机制了解甚少。被骨骼肌用作能量底物的L-乳酸也可以增强与代谢相关的基因表达，并上调对活性氧（ROS）有反应的基因。由于ROS是骨骼肌自噬的最重要调节剂，因此我们测试了分化的C2C12肌管和雄性wistar大鼠腓肠肌中细胞乳酸代谢与自噬之间是否存在联系。将C2C12小鼠骨骼肌暴露于2、6、10和20 mM乳酸中，并评估乳酸自噬作用。乳酸在不同的C2C12肌管中剂量依赖性地增加自噬并增加ROS的产生。在N-乙酰基半胱氨酸存在下抑制乳酸的自噬作用（NAC，一种ROS清除剂）表明，乳酸通过ROS参与调节自噬。乳酸需要通过乳酸诱导乳酸上调细胞外信号调节激酶1/2（ERK1 / 2），以调节自噬。对ERK1 / 2上下游的进一步分析表明，乳酸通过ROS介导骨骼肌ERK1 / 2 / mTOR / p70S6K途径的激活来调节自噬。乳酸对自噬的体外作用也发生在雄性Wistar大鼠的腓肠肌中。总之，我们通过激活ROS介导的ERK1 / 2 / mTOR / p70S6K途径，提供了与乳酸相关的骨骼肌自噬调节调控证据。由于细胞乳酸浓度的升高是能量缺乏的标志，