Sarcoplasmic reticulum-mitochondrial through-space coupling in skeletal muscle.
Sarcoplasmic reticulum-mitochondrial through-space coupling in skeletal muscle.
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DOI：
10.1139/h09-044
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发表时间：
2009-06
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影响因子：
--
通讯作者：
Dirksen RT
中科院分区：
文献类型：
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作者：
Dirksen RT
骨骼肌收缩机器由钙和ATP两者提供燃料。钙离子通过与肌钙蛋白C结合并解除肌钙蛋白-原肌球蛋白对放线肌球蛋白相互作用的抑制来激活收缩机制。在收缩周期中ATP与肌球蛋白结合导致肌球蛋白从肌动蛋白脱离，随后ATP水解释放的能量用于驱动下一个收缩周期。ATP还用于降低肌肉放松期间的肌浆钙水平。因此，肌肉收缩性与肌节Ca 2+递送/去除和ATP产生/利用的适当控制密切相关。在骨骼肌中，肌浆网（SR）是钙储存、释放和再摄取的主要调节器，而糖酵解和线粒体负责细胞ATP的产生。然而，肌肉中的SR和线粒体功能不是独立的，因为线粒体中的钙摄取通过刺激氧化磷酸化和线粒体ATP产生以及活性氧和氮物质（ROS/RNS）的产生/解毒来增加ATP产生，进而调节SR钙释放和再摄取。SR和线粒体之间的紧密空间Ca 2 +/ATP/ROS/RNS通信通过线粒体与钙释放单元（CRU）的结构连接（通过10 nm长的电子致密“系链”）来促进。由此产生的锚定线粒体的CRU提供了一个结构基础，以保持双向SR线粒体的“通过空间”通信在剧烈收缩。这篇评论将考虑在何种程度上这种结构的联系，使“特权”或“微域”之间的SR和线粒体在骨骼肌的通信。
The skeletal muscle contractile machine is fueled by both calcium and ATP. Calcium ions activate the contractile machinery by binding to troponin C and relieving troponin-tropomyosin inhibition of actinomyosin interaction. ATP binding to myosin during the contractile cycle results in myosin detachment from actin and energy liberated from subsequent ATP hydrolysis is then used to drive the next contractile cycle. ATP is also used to lower myoplasmic calcium levels during muscle relaxation. Thus, muscle contractility is intimately linked to the proper control of both sarcomeric Ca2+ delivery/removal and ATP generation/utilization. In skeletal muscle, the sarcoplasmic reticulum (SR) is the primary regulator of calcium storage, release, and reuptake while glycolysis and the mitochondria are responsible for cellular ATP production. However, the SR and mitochondrial function in muscle are not independent as calcium uptake into the mitochondria increases ATP production by stimulating oxidative phosphorylation and mitochondrial ATP production and production/detoxification of reactive oxygen and nitrogen species (ROS/RNS), in turn modulates SR calcium release and reuptake. Close spatial Ca2+/ATP/ROS/RNS communication between the SR and mitochondria is facilitated by the structural attachment of mitochondria to the calcium release unit (CRU) by 10 nm long electron dense “tethers.” The resultant anchoring of mitochondria to the CRU provides a structural basis for maintaining bi-directional SR-mitochondrial “through-space” communication during vigorous contraction. This review will consider the degree to which this structural link enables “privileged” or “microdomain” communication between the SR and mitochondria in skeletal muscle.