Protective Function of MCUb in Postischemic Remodeling Getting at the Heart of the Calcium Control Conundrum.
Protective Function of MCUb in Postischemic Remodeling Getting at the Heart of the Calcium Control Conundrum.
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MCUb 在缺血后重塑中的保护功能直击钙控制难题的核心。
DOI：
10.1161/circresaha.120.317423
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发表时间：
2020
影响因子：
20.1
通讯作者：
Gustafsson,ÅsaB
中科院分区：
文献类型：
--
作者：
Moyzis,AlexandraG;Gustafsson,ÅsaB
在心脏中，细胞内钙水平的严格调节对于维持细胞存活和心脏稳态是不可或缺的。钙是一种高度通用的信号分子，参与调节许多不同的过程，从线粒体代谢到心脏收缩。已知线粒体摄取钙，并且三羧酸循环中的许多线粒体酶是钙依赖性的。1然而，钙也有阴暗面，过量摄入会导致线粒体破坏并激活坏死细胞死亡。2线粒体钙超载导致线粒体通透性转换孔（mPTP）开放，允许溶质和水流入基质。这最终导致线粒体肿胀和破裂，并激活坏死细胞死亡。线粒体钙超载和mPTP开放发生在心肌缺血/再灌注（I/R）期间，是损伤的主要贡献者。[2]毫不奇怪，线粒体钙内流和外流都是高度调节的过程，对调节这些事件的机制的进一步理解可以为限制患者I/R损伤的治疗干预提供重要途径。
In the heart, rigorous regulation of intracellular calcium levels is integral to maintain cell survival and cardiac homeostasis. Calcium is a highly versatile signaling molecule that is involved in regulating many diverse processes, ranging from mitochondrial metabolism to cardiac contraction. Mitochondria are known to take up calcium, and many mitochondrial enzymes in the tricarboxylic acid cycle are calcium-dependent. 1 However, calcium also has a dark side where excess uptake can lead to destruction of mitochondria and activation of necrotic cell death. 2 Mitochondrial calcium overload leads to opening of the mitochondrial permeability transition pore (mPTP), allowing for the influx of solutes and water into the matrix. This ultimately causes mitochondrial swelling and rupture with activation of necrotic cell death. Mitochondrial calcium overload and mPTP opening occur during myocardial ischemia/reperfusion (I/R) and are major contributors to the injury. 2 Not surprisingly, both mitochondrial calcium influx and efflux are highly regulated processes and an increased understanding of the mechanisms regulating these events could provide important avenues for therapeutic intervention to limit I/R injury in patients.