Laboratory for Technologies of Advanced Therapies (LTTA), Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy.
Department of Neuroscience and Rehabilitation, University of Ferrara, 44121 Ferrara, Italy.
Cells. 2021 May 25;10(6):1317. doi: 10.3390/cells10061317.
The divalent cation calcium (Ca) is considered one of the main second messengers inside cells and acts as the most prominent signal in a plethora of biological processes. Its homeostasis is guaranteed by an intricate and complex system of channels, pumps, and exchangers. In this context, by regulating cellular Ca levels, mitochondria control both the uptake and release of Ca. Therefore, at the mitochondrial level, Ca plays a dual role, participating in both vital physiological processes (ATP production and regulation of mitochondrial metabolism) and pathophysiological processes (cell death, cancer progression and metastasis). Hence, it is not surprising that alterations in mitochondrial Ca (mCa) pathways or mutations in Ca transporters affect the activities and functions of the entire cell. Indeed, it is widely recognized that dysregulation of mCa signaling leads to various pathological scenarios, including cancer, neurological defects and cardiovascular diseases (CVDs). This review summarizes the current knowledge on the regulation of mCa homeostasis, the related mechanisms and the significance of this regulation in physiology and human diseases. We also highlight strategies aimed at remedying mCa dysregulation as promising therapeutical approaches.
二价阳离子钙 (Ca) 被认为是细胞内的主要第二信使之一，在众多生物过程中充当着最为显著的信号。其体内平衡由一个复杂而精巧的通道、泵和交换器系统来保证。在这种情况下，通过调节细胞内的 Ca 水平，线粒体可以控制 Ca 的摄取和释放。因此，在线粒体水平上，Ca 发挥着双重作用，参与了重要的生理过程（ATP 生成和线粒体代谢调节）和病理生理过程（细胞死亡、癌症进展和转移）。因此，线粒体 Ca（mCa）途径的改变或 Ca 转运体的突变会影响整个细胞的活性和功能，这并不奇怪。事实上，人们广泛认识到 mCa 信号的失调会导致各种病理情况，包括癌症、神经缺陷和心血管疾病（CVDs）。本综述总结了目前关于 mCa 稳态调节、相关机制以及这种调节在生理和人类疾病中的意义的知识。我们还强调了旨在纠正 mCa 失调的策略，这些策略是很有前途的治疗方法。
