Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, United Kingdom.
Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, United Kingdom.
Biochem Biophys Res Commun. 2018 May 27;500(1):75-86. doi: 10.1016/j.bbrc.2017.05.039. Epub 2017 May 8.
Mitochondria are dynamic organelles involved in numerous physiological functions. Beyond their function in ATP production, mitochondria regulate cell death, reactive oxygen species (ROS) generation, immunity and metabolism. Mitochondria also play a key role in the buffering of cytosolic calcium, and calcium transported into the matrix regulates mitochondrial metabolism. Recently, the identification of the mitochondrial calcium uniporter (MCU) and associated regulators has allowed the characterization of new physiological roles for calcium in both mitochondrial and cellular homeostasis. Indeed, recent work has highlighted the importance of mitochondrial calcium homeostasis in regulating cell migration. Cell migration is a property common to all metazoans and is critical to embryogenesis, cancer progression, wound-healing and immune surveillance. Previous work has established that cytoplasmic calcium is a key regulator of cell migration, as oscillations in cytosolic calcium activate cytoskeletal remodelling, actin contraction and focal adhesion (FA) turnover necessary for cell movement. Recent work using animal models and in cellulo experiments to genetically modulate MCU and partners have shed new light on the role of mitochondrial calcium dynamics in cytoskeletal remodelling through the modulation of ATP and ROS production, as well as intracellular calcium signalling. This review focuses on MCU and its regulators in cell migration during physiological and pathophysiological processes including development and cancer. We also present hypotheses to explain the molecular mechanisms by which MCU may regulate mitochondrial dynamics and motility to drive cell migration.
线粒体是参与多种生理功能的动态细胞器。除了在 ATP 产生中的作用外，线粒体还调节细胞死亡、活性氧 (ROS) 的产生、免疫和代谢。线粒体在细胞溶质钙缓冲中也起着关键作用，进入基质的钙调节线粒体代谢。最近，线粒体钙单向转运蛋白 (MCU) 和相关调节剂的鉴定允许对钙在线粒体和细胞内稳态中的新生理作用进行特征描述。事实上，最近的工作强调了线粒体钙稳态在调节细胞迁移中的重要性。细胞迁移是所有后生动物的共同特性，对胚胎发生、癌症进展、伤口愈合和免疫监视至关重要。以前的工作已经确定细胞质钙是细胞迁移的关键调节剂，因为细胞质钙的振荡激活细胞骨架重塑，肌动蛋白收缩和焦点黏附 (FA) 周转是细胞运动所必需的。最近使用动物模型和细胞内实验来遗传调节 MCU 和伙伴的工作，通过调节 ATP 和 ROS 的产生以及细胞内钙信号，揭示了线粒体钙动力学在细胞骨架重塑中的作用。本综述重点介绍了在生理和病理生理过程（包括发育和癌症）中细胞迁移中的 MCU 及其调节剂。我们还提出了假设，以解释 MCU 可能调节线粒体动力学和运动以驱动细胞迁移的分子机制。
