Mitochondria are cellular factories for energy production, calcium homeostasis and iron metabolism, but they also have an unequivocal and central role in intrinsic apoptosis through the release of cytochrome c. While the subsequent activation of proteolytic caspases ensures that cell death proceeds in the absence of collateral inflammation, other phlogistic cell death pathways have been implicated in using, or engaging, mitochondria. Here we discuss the emerging complexities of intrinsic apoptosis controlled by the BCL-2 family of proteins. We highlight the emerging theory that non-lethal mitochondrial apoptotic signalling has diverse biological roles that impact cancer, innate immunity and ageing. Finally, we delineate the role of mitochondria in other forms of cell death, such as pyroptosis, ferroptosis and necroptosis, and discuss mitochondria as central hubs for the intersection and coordination of cell death signalling pathways, underscoring their potential for therapeutic manipulation.

线粒体是能量生产、钙稳态和铁代谢的细胞工厂，但它们还通过释放细胞色素c在内在细胞凋亡中发挥着明确的核心作用。虽然随后蛋白水解半胱天冬酶的激活确保细胞死亡在没有附带炎症的情况下进行，但其他炎性细胞死亡途径也与线粒体的使用或参与有关。在这里，我们讨论由 BCL-2 蛋白家族控制的内在细胞凋亡的新出现的复杂性。我们强调了一个新兴理论，即非致命性线粒体凋亡信号传导具有影响癌症、先天免疫和衰老的多种生物学作用。最后，我们描述了线粒体在其他形式的细胞死亡中的作用，例如焦亡、铁死亡和坏死性凋亡，并讨论线粒体作为细胞死亡信号通路交叉和协调的中枢，强调了它们在治疗操纵方面的潜力。