CAST, Center for Advanced Studies and Technology, University G. d'Annunzio of Chieti-Pescara, I-66100 Chieti, Italy.
DMSI, Department of Medicine and Aging Sciences, University G. d'Annunzio of Chieti-Pescara, I-66100 Chieti, Italy.
Int J Mol Sci. 2021 Jun 8;22(12):6195. doi: 10.3390/ijms22126195.
Proper skeletal muscle function is controlled by intracellular Ca concentration and by efficient production of energy (ATP), which, in turn, depend on: (a) the release and re-uptake of Ca from sarcoplasmic-reticulum (SR) during excitation-contraction (EC) coupling, which controls the contraction and relaxation of sarcomeres; (b) the uptake of Ca into the mitochondrial matrix, which stimulates aerobic ATP production; and finally (c) the entry of Ca from the extracellular space via store-operated Ca entry (SOCE), a mechanism that is important to limit/delay muscle fatigue. Abnormalities in Ca handling underlie many physio-pathological conditions, including dysfunction in ageing. The specific focus of this review is to discuss the importance of the proper architecture of organelles and membrane systems involved in the mechanisms introduced above for the correct skeletal muscle function. We reviewed the existing literature about EC coupling, mitochondrial Ca uptake, SOCE and about the structural membranes and organelles deputed to those functions and finally, we summarized the data collected in different, but complementary, projects studying changes caused by denervation and ageing to the structure and positioning of those organelles: a. denervation of muscle fibers-an event that contributes, to some degree, to muscle loss in ageing (known as sarcopenia)-causes misplacement and damage: (i) of membrane structures involved in EC coupling (calcium release units, CRUs) and (ii) of the mitochondrial network; b. sedentary ageing causes partial disarray/damage of CRUs and of calcium entry units (CEUs, structures involved in SOCE) and loss/misplacement of mitochondria; c. functional electrical stimulation (FES) and regular exercise promote the rescue/maintenance of the proper architecture of CRUs, CEUs, and of mitochondria in both denervation and ageing. All these structural changes were accompanied by related functional changes, i.e., loss/decay in function caused by denervation and ageing, and improved function following FES or exercise. These data suggest that the integrity and proper disposition of intracellular organelles deputed to Ca handling and aerobic generation of ATP is challenged by inactivity (or reduced activity); modifications in the architecture of these intracellular membrane systems may contribute to muscle dysfunction in ageing and sarcopenia.
适当的骨骼肌肉功能受细胞内 Ca 浓度和有效能量（ATP）产生的控制，而这反过来又取决于：（a）兴奋-收缩（EC）偶联期间肌浆网（SR）中 Ca 的释放和再摄取，控制肌节的收缩和松弛；（b）Ca 进入线粒体基质，刺激有氧 ATP 产生；最后（c）通过储存操作的 Ca 进入（SOCE）从细胞外空间进入 Ca，这一机制对于限制/延迟肌肉疲劳很重要。Ca 处理异常是许多生理病理条件的基础，包括衰老功能障碍。本综述的重点是讨论上述机制中涉及的细胞器和膜系统的适当结构对于正确的骨骼肌肉功能的重要性。我们回顾了关于 EC 偶联、线粒体 Ca 摄取、SOCE 以及负责这些功能的结构膜和细胞器的现有文献，最后总结了在不同但互补的项目中收集的数据，这些项目研究了去神经和衰老对这些细胞器的结构和定位的影响：a. 肌肉纤维去神经-这一事件在一定程度上导致衰老过程中的肌肉损失（称为肌肉减少症）-导致错位和损伤：（i）EC 偶联涉及的膜结构（钙释放单位，CRU）和（ii）线粒体网络；b. 久坐不动的衰老导致 CRU 和钙进入单位（CEU，参与 SOCE 的结构）的部分混乱/损伤以及线粒体的损失/错位；c. 功能性电刺激（FES）和定期运动促进 CRU、CEU 和线粒体在去神经和衰老中的适当结构的挽救/维持。所有这些结构变化都伴随着相关的功能变化，即去神经和衰老引起的功能丧失/衰减，以及 FES 或运动后的功能改善。这些数据表明，细胞内细胞器的完整性和适当配置负责 Ca 处理和有氧生成 ATP 受到不活动（或活动减少）的挑战；这些细胞内膜系统的结构改变可能导致衰老和肌肉减少症中的肌肉功能障碍。
