Cancer Research UK Scotland Institute, Glasgow, UK.
School of Cancer Sciences, University of Glasgow, Glasgow, UK.
Nat Cell Biol. 2024 Sep;26(9):1434-1446. doi: 10.1038/s41556-024-01429-4. Epub 2024 Jun 20.
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.
线粒体是细胞能量产生、钙稳态和铁代谢的工厂,但它们通过释放细胞色素 c 也在内在凋亡中具有明确且核心的作用。虽然随后激活的蛋白水解半胱天冬酶确保了在没有附带炎症的情况下进行细胞死亡,但其他炎症性细胞死亡途径也被认为与线粒体的使用或参与有关。在这里,我们讨论了由 BCL-2 蛋白家族控制的内在凋亡的新出现的复杂性。我们强调了一个新的理论,即非致死性线粒体凋亡信号具有多种生物学作用,影响癌症、先天免疫和衰老。最后,我们描述了线粒体在其他细胞死亡形式(如细胞焦亡、铁死亡和坏死性凋亡)中的作用,并讨论了线粒体作为细胞死亡信号通路交叉和协调的中心枢纽,突出了它们在治疗干预方面的潜力。
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