Skeletal muscle mitochondria are placed in close proximity of the sarcoplasmic reticulum (SR), the main intracellular Ca^2 + store. During muscle activity, excitation of sarcolemma and of T-tubule triggers the release of Ca^2 + from the SR initiating myofiber contraction. The rise in cytosolic Ca^2 + determines the opening of the mitochondrial calcium uniporter (MCU), the highly selective channel of the inner mitochondrial membrane (IMM), causing a robust increase in mitochondrial Ca^2 + uptake. The Ca^2 +-dependent activation of TCA cycle enzymes increases the synthesis of ATP required for SERCA activity. Thus, Ca^2 + is transported back into the SR and cytosolic [Ca^2 +] returns to resting levels eventually leading to muscle relaxation. In recent years, thanks to the molecular identification of MCU complex components, the role of mitochondrial Ca^2 + uptake in the pathophysiology of skeletal muscle has been uncovered. In this chapter, we will introduce the reader to a general overview of mitochondrial Ca^2 + accumulation. We will tackle the key molecular players and the cellular and pathophysiological consequences of mitochondrial Ca^2 + dyshomeostasis. In the second part of the chapter, we will discuss novel findings on the physiological role of mitochondrial Ca^2 + uptake in skeletal muscle. Finally, we will examine the involvement of mitochondrial Ca^2 + signaling in muscle diseases.

骨骼肌线粒体紧邻肌质网 (SR)，这是细胞内主要的 Ca ^{2  +}储存。在肌肉活动期间，肌膜和 T 小管的兴奋会触发 Ca ^{2  +}从 SR 释放，从而引发肌纤维收缩。^{细胞溶质 Ca 2  +}的升高决定了线粒体钙单向转运体 (MCU) 的打开，MCU 是线粒体内膜 (IMM) 的高选择性通道，导致线粒体 Ca ^{2  +}摄取的强劲增加。TCA循环酶的Ca ^{2  +}依赖性激活增加了SERCA活性所需的ATP合成。因此，Ca ^{2  +}被转运回 SR 和细胞溶质 [Ca ^{2  +} ] 恢复到静息水平，最终导致肌肉松弛。近年来，通过对MCU复合成分的分子鉴定，揭示了线粒体Ca ^2+摄取 在骨骼肌病理生理中的作用。在本章中，我们将向读者介绍线粒体 Ca ^{2  +}积累的一般概述。我们将解决关键分子参与者以及线粒体 Ca ^{2  +}失调的细胞和病理生理学后果。在本章的第二部分，我们将讨论关于线粒体 Ca ^{2  +生理作用的新发现。}骨骼肌摄取。最后，我们将检查线粒体 Ca ^{2  +}信号传导在肌肉疾病中的作用。