Departments of Physiology and Biophysics, Dalhousie University, Halifax, NS, Canada.
Adv Exp Med Biol. 2020;1131:747-770. doi: 10.1007/978-3-030-12457-1_30.
The pioneering work of Richard Altman on the presence of mitochondria in cells set in motion a field of research dedicated to uncovering the secrets of the mitochondria. Despite limitations in studying the structure and function of the mitochondria, advances in our understanding of this organelle prompted the development of potential treatments for various diseases, from neurodegenerative conditions to muscular dystrophy and cancer. As the powerhouses of the cell, the mitochondria represent the essence of cellular life and as such, a selective advantage for cancer cells. Much of the function of the mitochondria relies on Ca homeostasis and the presence of effective Ca signaling to maintain the balance between mitochondrial function and dysfunction and subsequently, cell survival. Ca regulates the mitochondrial respiration rate which in turn increases ATP synthesis, but too much Ca can also trigger the mitochondrial apoptosis pathway; however, cancer cells have evolved mechanisms to modulate mitochondrial Ca influx and efflux in order to sustain their metabolic demand and ensure their survival. Therefore, targeting the mitochondrial Ca signaling involved in the bioenergetic and apoptotic pathways could serve as potential approaches to treat cancer patients. This chapter will review the role of Ca signaling in mediating the function of the mitochondria and its involvement in health and disease with special focus on the pathophysiology of cancer.
理查德·奥尔特曼（Richard Altman）在细胞中线粒体存在方面的开创性工作引发了一个专门研究揭示线粒体秘密的研究领域。尽管在研究线粒体的结构和功能方面存在局限性，但我们对该细胞器的理解的进步促使人们开发出了针对各种疾病的潜在治疗方法，从神经退行性疾病到肌肉营养不良症和癌症。作为细胞的“动力源”，线粒体代表了细胞生命的本质，因此是癌细胞的选择性优势。线粒体的许多功能依赖于 Ca 离子稳态和有效的 Ca 信号转导，以维持线粒体功能和功能障碍之间的平衡，从而维持细胞存活。Ca 离子调节线粒体呼吸速率，从而增加 ATP 合成，但过多的 Ca 离子也会触发线粒体凋亡途径；然而，癌细胞已经进化出调节线粒体 Ca 内流和外流的机制，以维持其代谢需求并确保其存活。因此，靶向参与生物能量和凋亡途径的线粒体 Ca 信号转导可能成为治疗癌症患者的潜在方法。本章将回顾 Ca 信号转导在调节线粒体功能及其在健康和疾病中的作用，特别关注癌症的病理生理学。
