Department of Chronic-Degenerative Diseases, National Institute of Respiratory Diseases 'Ismael Cosío Villegas', CP 14080 Mexico City, Mexico.
Int J Oncol. 2019 Apr;54(4):1155-1167. doi: 10.3892/ijo.2019.4696. Epub 2019 Jan 28.
In addition to their role in providing cellular energy, mitochondria fulfill a key function in cellular calcium management. The present review provides an integrative view of cellular and mitochondrial calcium homeostasis, and discusses how calcium regulates mitochondrial dynamics and functionality, thus affecting various cellular processes. Calcium crosstalk exists in the domain created between the endoplasmic reticulum and mitochondria, which is known as the mitochondria‑associated membrane (MAM), and controls cellular homeostasis. Calcium signaling participates in numerous biochemical and cellular processes, where calcium concentration, temporality and durability are part of a regulated, finely tuned interplay in non‑transformed cells. In addition, cancer cells modify their MAMs, which consequently affects calcium homeostasis to support mesenchymal transformation, migration, invasiveness, metastasis and autophagy. Alterations in calcium homeostasis may also support resistance to apoptosis, which is a serious problem facing current chemotherapeutic treatments. Notably, mitochondrial dynamics are also affected by mitochondrial calcium concentration to promote cancer survival responses. Dysregulated levels of mitochondrial calcium, alongside other signals, promote mitoflash generation in tumor cells, and an increased frequency of mitoflashes may induce epithelial‑to‑mesenchymal transition. Therefore, cancer cells remodel their calcium balance through numerous mechanisms that support their survival and growth.
除了为细胞提供能量外，线粒体还在细胞钙管理中发挥关键作用。本综述提供了细胞和线粒体钙稳态的综合观点，并讨论了钙如何调节线粒体动力学和功能，从而影响各种细胞过程。钙信号存在于内质网和线粒体之间形成的区域，即线粒体相关膜（MAM），并控制细胞内稳态。钙信号参与许多生化和细胞过程，其中钙浓度、时间性和持久性是未转化细胞中受调控的精细相互作用的一部分。此外，癌细胞改变它们的 MAMs，这反过来又影响钙稳态以支持间充质转化、迁移、侵袭、转移和自噬。钙稳态的改变也可能支持对细胞凋亡的抵抗，这是当前化疗治疗面临的一个严重问题。值得注意的是，线粒体钙浓度也会影响线粒体动力学，以促进癌症存活反应。线粒体钙水平的失调，以及其他信号，会促进肿瘤细胞中产生线粒体闪烁，而线粒体闪烁频率的增加可能会诱导上皮-间充质转化。因此，癌细胞通过多种机制重塑其钙平衡，以支持其存活和生长。
