Autophagy is one of the major cellular degradation pathways, which prevents accumulation of cellular wastes including "hazardous" material such as oxidized proteins and lipids and allows removal of aggregates and dysfunctional organelles. Hence, autophagy is meant to preserve cell survival, and is mostly protective. However, autophagy may trigger a feedforward, exaggerated cycle in which cells continue to degrade proteins and organelles, finally leading to autophagy-dependent cell death (ADCD), a process that can be initiated with lysosomotropic detergents, which are protonated within the lysosome and cause a permeabilization of the membrane. Such drugs may be useful to combat cancer. In some paradigms of ADCD, there is evidence that the cellular fate is determined by the integrity of lysosomal membranes, transporters, enzymes and ion gradients. Detergent-like effects of lysosomotropic drugs can over-activate autophagy. A disruption of the lysosomal membrane barrier with leakage of lysosomal enzymes or lipids may trigger a vicious cycle via proteases and accumulation of lipids, which impair the functions of the plasma - and organelle membranes. This review summarizes the current evidence for a crosstalk between lysosomal dysfunction and autophagy and the lysosomal events, which progress toward ADCD with a focus on the role of sphingolipids and cholesterol as cargo and as regulators of ADCD.

自噬是主要的细胞降解途径之一，它可以防止细胞废物的积累，包括氧化蛋白质和脂质等“有害”物质，并允许去除聚集体和功能失调的细胞器。因此，自噬旨在保护细胞存活，并且主要是保护性的。然而，自噬可能触发一个前馈的、夸张的循环，在这个循环中细胞继续降解蛋白质和细胞器，最终导致自噬依赖性细胞死亡 (ADCD)，这一过程可以用溶酶体去污剂启动，这些去污剂在溶酶体内质子化并导致膜的透化。这些药物可能有助于对抗癌症。在 ADCD 的一些范例中，有证据表明细胞命运是由溶酶体膜、转运蛋白、酶和离子梯度。溶酶体药物的洗涤剂样作用会过度激活自噬。溶酶体膜屏障的破坏与溶酶体酶或脂质的泄漏可能会通过蛋白酶和脂质的积累引发恶性循环，这会损害质膜和细胞器膜的功能。这篇综述总结了溶酶体功能障碍和自噬与溶酶体事件之间的串扰的当前证据，这些证据向 ADCD 发展，重点是鞘脂和胆固醇作为货物和作为 ADCD 调节剂的作用。这会损害质膜和细胞器膜的功能。这篇综述总结了溶酶体功能障碍和自噬与溶酶体事件之间的串扰的当前证据，这些证据向 ADCD 发展，重点是鞘脂和胆固醇作为货物和作为 ADCD 调节剂的作用。这会损害质膜和细胞器膜的功能。这篇综述总结了溶酶体功能障碍和自噬与溶酶体事件之间的串扰的当前证据，这些证据向 ADCD 发展，重点是鞘脂和胆固醇作为货物和作为 ADCD 调节剂的作用。