Centre for Cancer Biology, University of South Australia and SA Pathology, GPO Box 2471, Adelaide, SA, 5001, Australia.
Cell Death Differ. 2019 Mar;26(4):605-616. doi: 10.1038/s41418-018-0252-y. Epub 2018 Dec 19.
Autophagy-dependent cell death can be defined as cell demise that has a strict requirement of autophagy. Although autophagy often accompanies cell death following many toxic insults, the requirement of autophagic machinery for cell death execution, as established through specific genetic or chemical inhibition of the process, is highly contextual. During animal development, perhaps the best validated model of autophagy-dependent cell death is the degradation of the larval midgut during larval-pupal metamorphosis, where a number of key autophagy genes are required for the removal of the tissues. Surprisingly though, even in the midgut, not all of the 'canonical' autophagic machinery appears to be required. In other organisms and cancer cells many variations of autophagy-dependent cell death are apparent, pointing to the lack of a unifying cell death pathway. It is thus possible that components of the autophagy machinery are selectively utilised or repurposed for this type of cell death. In this review, we discuss examples of cell death that utilise autophagy machinery (or part thereof), the current knowledge of the complexity of autophagy-dependent cellular demise and the potential mechanisms and regulatory pathways involved in such cell death.
自噬依赖性细胞死亡可以被定义为严格依赖自噬的细胞死亡。虽然自噬通常伴随着许多毒性损伤后的细胞死亡，但自噬机制对细胞死亡执行的需求，如通过特定的遗传或化学抑制过程来建立，具有高度的背景依赖性。在动物发育过程中，自噬依赖性细胞死亡的最佳验证模型可能是幼虫中肠在幼虫-蛹变态期间的降解，在此过程中，许多关键的自噬基因被需要用于组织的去除。然而，令人惊讶的是，即使在中肠中，似乎也不需要所有的“经典”自噬机制。在其他生物体和癌细胞中，自噬依赖性细胞死亡的许多变体是明显的，这表明缺乏统一的细胞死亡途径。因此，自噬机制的成分可能被选择性地用于或重新用于这种类型的细胞死亡。在这篇综述中，我们讨论了利用自噬机制（或其一部分）的细胞死亡的例子，目前对自噬依赖性细胞死亡的复杂性的认识，以及涉及这种细胞死亡的潜在机制和调节途径。
