Department of Physiology and Pennsylvania Muscle Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
J Cell Sci. 2018 Nov 2;131(21):jcs218313. doi: 10.1242/jcs.218313.
The pro-inflammatory cytokine interleukin-15 (IL15) and its receptor α (IL15RA) participate in the regulation of musculoskeletal function and metabolism. Deletion of the gene in mice increases spontaneous activity, improves fatigue resistance in the glycolytic extensor digitorum longus (EDL) and protects from diet-induced obesity. In humans, single-nucleotide polymorphisms (SNPs) have been linked to muscle strength, metabolism and performance in elite endurance athletes. Taken together, these features suggest a possible role for IL15RA in muscle mitochondrial structure and function. Here, we have investigated the consequences of loss of IL15RA on skeletal muscle fiber-type properties and mitochondrial ultrastructure. Immunostaining of the EDL for myosin heavy chain (MyHC) isoforms revealed no significant changes in fiber type. Electron microscopy (EM) analysis of the EDL indicated an overall higher mitochondria content, and increased cristae density in subsarcolemmal and A-band mitochondrial subpopulations. The higher cristae density in mitochondria was associated with higher OPA1 and cardiolipin levels. Overall, these data extend our understanding of the role of IL15RA signaling in muscle oxidative metabolism and adaptation to exercise.
促炎细胞因子白细胞介素-15（IL-15）及其受体α（IL-15RA）参与调节肌肉骨骼功能和代谢。在小鼠中删除该基因可增加自发性活动，提高糖酵解伸肌（EDL）的抗疲劳能力，并防止饮食诱导的肥胖。在人类中，单核苷酸多态性（SNP）与肌肉力量、代谢和精英耐力运动员的表现有关。综上所述，这些特征表明 IL-15RA 可能在肌肉线粒体结构和功能中发挥作用。在这里，我们研究了缺失 IL-15RA 对骨骼肌纤维类型特性和线粒体超微结构的影响。EDL 肌球蛋白重链（MyHC）同工型的免疫染色显示纤维类型没有明显变化。EDL 的电子显微镜（EM）分析表明，总体线粒体含量较高，亚肌小节和 A 带线粒体亚群的嵴密度增加。线粒体中较高的嵴密度与较高的 OPA1 和心磷脂水平相关。总的来说，这些数据扩展了我们对 IL-15RA 信号在肌肉氧化代谢和对运动适应中的作用的理解。
