Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel
J Cell Sci. 2018 Sep 20;131(18):jcs215152. doi: 10.1242/jcs.215152.
Autophagy as a means of cell killing was first advanced by Clark's phenotypic description of 'Type II autophagic cell death' in 1990. However, this phenomenon later came into question, because the presence of autophagosomes in dying cells does not necessarily signify that autophagy is the cause of demise, but rather may reflect the efforts of the cell to prevent it. Resolution of this issue comes from a more careful definition of autophagy-dependent cell death (ADCD) as a regulated cell death that is shown experimentally to require different components of the autophagy machinery without involvement of alternative cell death pathways. Following these strict criteria, ADCD has been validated in both lower model organisms and mammalian cells, highlighting its importance for developmental and pathophysiological cell death. Recently, researchers have defined additional morphological criteria that characterize ADCD and begun to explore how the established, well-studied autophagy pathway is subverted from a survival to a death function. This Review explores validated models of ADCD and focuses on the current understanding of the mechanisms by which autophagy can kill a cell.
自噬作为一种细胞杀伤方式，最早是由 Clark 在 1990 年对“II 型自噬性细胞死亡”的表型描述中提出的。然而，这一现象后来受到了质疑，因为在濒死细胞中存在自噬体并不一定表明自噬是导致死亡的原因，而可能反映了细胞为了防止死亡所做的努力。解决这个问题的关键在于对自噬依赖性细胞死亡（ADCD）进行更仔细的定义，即一种受调控的细胞死亡，实验表明其需要自噬机制的不同成分，而不涉及其他细胞死亡途径。根据这些严格的标准，ADCD 在低等模式生物和哺乳动物细胞中都得到了验证，突出了其在发育和病理生理学细胞死亡中的重要性。最近，研究人员定义了 ADCD 的其他形态学标准，并开始探索已建立的、研究充分的自噬途径如何从生存功能转变为死亡功能。本综述探讨了 ADCD 的验证模型，并重点介绍了目前对自噬如何杀死细胞的机制的理解。
