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 Ca²⁺ homeostasis, especially by the joint participation of the endoplasmic reticulum in a membranous tethering system for Ca²⁺ 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定中具有双重作用。这适用于所有细胞类型，但在癌症环境中更为重要和有趣。

线粒体以多种不同的方式调节细胞命运：通过新陈代谢、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 ²⁺稳态，特别是通过内质网共同参与称为线粒体-ER 相关膜 (MAM) 的Ca ²⁺信号传导系统；并通过调节参与癌细胞存活的信号通路，如线粒体自噬。最近的研究表明，线粒体还可以在癌细胞炎症通路的调节中发挥作用，例如，通过释放参与 cGAS-cGAMP-STING 通路激活的线粒体 DNA (mtDNA)。

在这篇综述中，我们旨在探索线粒体作为决策者在促进癌细胞死亡或存活取决于肿瘤细胞阶段方面的作用，并描述针对线粒体的新型抗癌治疗策略。