Department of Medical Sciences, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
ENT & Audiology Department, University Hospital of Ferrara, Ferrara, Italy.
Cell Calcium. 2020 Dec;92:102308. doi: 10.1016/j.ceca.2020.102308. Epub 2020 Oct 16.
As pivotal players in cellular metabolism, mitochondria have a double-faceted role in the final decision of cell fate. This is true for all cell types, but it is even more important and intriguing in the cancer setting. Mitochondria regulate cell fate in many diverse ways: through metabolism, by producing ATP and other metabolites deemed vital or detrimental for cancer cells; through the regulation of Ca homeostasis, especially by the joint participation of the endoplasmic reticulum in a membranous tethering system for Ca signaling called mitochondria-ER associated membranes (MAMs); and by regulating signaling pathways involved in the survival of cancer cells such as mitophagy. Recent studies have shown that mitochondria can also play a role in the regulation of inflammatory pathways in cancer cells, for example, through the release of mitochondrial DNA (mtDNA) involved in the activation of the cGAS-cGAMP-STING pathway. In this review, we aim to explore the role of mitochondria as decision makers in fostering cancer cell death or survival depending on the tumor cell stage and describe novel anticancer therapeutic strategies targeting mitochondria.
作为细胞代谢的关键参与者，线粒体在细胞命运的最终决策中具有双重作用。这对于所有类型的细胞都是如此，但在癌症环境中更为重要和有趣。线粒体通过多种不同的方式调节细胞命运：通过代谢，产生 ATP 和其他被认为对癌细胞至关重要或有害的代谢物；通过调节 Ca 稳态，特别是通过内质网（ER）参与称为线粒体-内质网相关膜（MAMs）的 Ca 信号传导的膜结合系统；通过调节参与癌细胞存活的信号通路，例如自噬。最近的研究表明，线粒体还可以在癌细胞中炎症途径的调节中发挥作用，例如，通过释放参与 cGAS-cGAMP-STING 途径激活的线粒体 DNA（mtDNA）。在这篇综述中，我们旨在探讨线粒体作为决定因素在促进癌细胞死亡或存活中的作用，具体取决于肿瘤细胞的阶段，并描述针对线粒体的新型抗癌治疗策略。
