The good, the bad and the autophagosome: exploring unanswered questions of autophagy-dependent cell death.,Cell Death and Differentiation

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The good, the bad and the autophagosome: exploring unanswered questions of autophagy-dependent cell death.
Cell Death and Differentiation ( IF 13.7 ) Pub Date : 2019-01-18 , DOI: 10.1038/s41418-018-0267-4
Jurgen Kriel ₁ , Ben Loos ₁

Affiliation

The recent discovery of autosis as a variant of autophagy-dependent cell death has challenged the conventional understanding of cell death and programmed cell death in cellular decision making. In contrast to previous accounts of distinct cell death modalities, autosis occurs with high autophagic activity, in the absence of apoptotic and necrotic markers and yet is not fully regulated by typical autophagy markers. Given the metabolic importance of autophagic responses and the extensive cross-talk with both apoptosis and necrosis signalling, the classical and morphotype-driven characterization of cell death as pre-determined subroutines is being increasingly called into question. Furthermore, the conflicting evidence with regards to cell death induction through autophagy modulation in various cancer models highlights the lack of consensus over the extent to which autophagy assists in cell death ontrol and whether it is capable of being a bona fide lethal process. This review evaluates the evidence and context of autophagy-dependent cell death and delineates the role of an autophagic flux threshold associated with 'lethal' and 'non-lethal' autophagy and its role in autosis control. In doing so, cancer treatment avenues will be explored with regards to precision modulation of tumour autophagic flux to ascertain whether autosis induction may present a novel therapeutic strategy.

中文翻译：

好的、坏的和自噬体：探索自噬依赖性细胞死亡的未解答问题。

最近发现自噬是自噬依赖性细胞死亡的一种变体，这挑战了细胞决策中细胞死亡和程序性细胞死亡的传统理解。与之前对不同细胞死亡方式的描述相反，自噬在缺乏凋亡和坏死标记的情况下以高自噬活性发生，但不受典型自噬标记的完全调节。鉴于自噬反应的代谢重要性以及与细胞凋亡和坏死信号传导的广泛交叉，细胞死亡作为预定子程序的经典和形态类型驱动的表征越来越受到质疑。此外，关于各种癌症模型中通过自噬调节诱导细胞死亡的相互矛盾的证据突显出，对于自噬在细胞死亡控制中的协助程度以及它是否能够成为真正的致死过程，缺乏共识。本综述评估了自噬依赖性细胞死亡的证据和背景，并描述了与“致死”和“非致死”自噬相关的自噬通量阈值的作用及其在自噬控制中的作用。在此过程中，将探索精确调节肿瘤自噬流的癌症治疗途径，以确定自噬诱导是否可以提供一种新的治疗策略。

更新日期：2019-01-26

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