W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
FEBS J. 2020 Jul;287(13):2647-2663. doi: 10.1111/febs.15308. Epub 2020 Apr 11.
Apoptosis is a highly regulated form of cell death that is required for many homeostatic and pathological processes. Recently, alternative cell death pathways have emerged whose regulation is dependent on proteins with canonical functions in apoptosis. Dysregulation of apoptotic signaling frequently underlies the pathogenesis of many cancers, reinforcing the need to develop therapies that initiate alternative cell death processes. This review outlines the convergence points between apoptosis and other death pathways with the purpose of identifying novel strategies for the treatment of apoptosis-refractory cancers. Apoptosis proteins can play key roles in the initiation, regulation, and execution of nonapoptotic death processes that include necroptosis, autophagy, pyroptosis, mPTP-mediated necrosis, and ferroptosis. Notably, recent evidence illustrates that dying cells can exhibit biochemical and molecular characteristics of more than one different type of regulated cell death. Thus, this review highlights the amazing complexity and interconnectivity of cell death processes and also raises the idea that a top-to-bottom approach to describing cell death mechanisms may be inadequate for fully understanding the means by which cells die.
细胞凋亡是一种高度受调控的细胞死亡形式，对于许多体内平衡和病理过程都是必需的。最近，出现了其他细胞死亡途径，其调控依赖于在细胞凋亡中具有典型功能的蛋白质。凋亡信号的失调常常是许多癌症发病机制的基础，这就需要开发能够引发其他细胞死亡过程的治疗方法。本综述概述了细胞凋亡与其他死亡途径的交汇点，目的是确定治疗对细胞凋亡有抗性的癌症的新策略。凋亡蛋白在起始、调节和执行非凋亡性死亡过程中起着关键作用，包括坏死性凋亡、自噬、细胞焦亡、mPTP 介导的坏死和铁死亡。值得注意的是，最近的证据表明，死亡细胞可以表现出一种以上不同类型的受调控细胞死亡的生化和分子特征。因此，本综述强调了细胞死亡过程的惊人复杂性和相互关联性，并提出了自上而下描述细胞死亡机制的方法可能不足以完全理解细胞死亡的方式的观点。
