The conserved catabolic process of autophagy is an important control mechanism that degrades cellular organelles, debris and pathogens in autolysosomes. Although autophagy primarily protects against cellular insults, nutrient starvation or oxidative stress, hyper-activation of autophagy is also believed to cause autophagy-dependent cell death (ADCD). ADCD is a caspase-independent form of programmed cell death (PCD), characterized by an over-activation of autophagy, leading to prominent self-digestion of cellular material in autolysosomes beyond the point of cell survival. ADCD plays important roles in the development of lower organisms, but also in the response of cancer cells upon exposure of specific drugs or natural compounds. Importantly, the induction of ADCD as an alternative cell death pathway is of special interest in apoptosis-resistant cancer types and serves as an attractive and potential therapeutic option. Although the mechanisms of ADCD are diverse and not yet fully understood, both non-selective (bulk) autophagy and organelle-specific types of autophagy are believed to be involved in this type of cell death. Accordingly, several ADCD-inducing drugs are known to trigger severe mitochondrial damage and endoplasmic reticulum (ER) stress, whereas the contribution of other cell organelles, like ribosomes or peroxisomes, to the control of ADCD is not well understood. In this review, we highlight the general mechanisms of ADCD and discuss the current evidence for mitochondria- and ER-specific killing mechanisms of ADCD-inducing drugs.

自噬的保守分解代谢过程是降解自溶酶体中细胞器、碎片和病原体的重要控制机制。尽管自噬主要防止细胞损伤、营养缺乏或氧化应激，但自噬的过度激活也被认为会导致自噬依赖性细胞死亡 (ADCD)。ADCD 是一种不依赖半胱天冬酶的程序性细胞死亡 (PCD) 形式，其特征是自噬过度激活，导致自溶酶体中细胞物质的显着自我消化超出细胞存活点。ADCD 在低等生物的发育中发挥重要作用，而且在癌细胞对特定药物或天然化合物的反应中也发挥着重要作用。重要的，诱导ADCD作为一种替代性细胞死亡途径对抗凋亡的癌症类型特别感兴趣，并作为一种有吸引力和潜在的治疗选择。尽管 ADCD 的机制多种多样且尚未完全了解，但据信非选择性（大量）自噬和细胞器特异性类型的自噬都与这种类型的细胞死亡有关。因此，已知几种诱导 ADCD 的药物会引发严重的线粒体损伤和内质网 (ER) 应激，而其他细胞器（如核糖体或过氧化物酶体）对 ADCD 控制的贡献尚不清楚。在这篇综述中，我们重点介绍了 ADCD 的一般机制，并讨论了 ADCD 诱导药物的线粒体和 ER 特异性杀伤机制的当前证据。