Mohseni Nilufar, McMillan Stephanie C, Chaudhary Roopali, Mok Jane, Reed Bruce H
Department of Biology, University of Waterloo, Waterloo, Ontario, Canada.
Autophagy. 2009 Apr;5(3):329-38. doi: 10.4161/auto.5.3.7444. Epub 2009 Apr 19.
The relationship between autophagic cell death and apoptosis is a poorly understood aspect of programmed cell death (PCD). We have examined this relationship by studying the elimination of an extra-embryonic tissue, known as the amnioserosa (AS), during Drosophila development. The AS becomes autophagic during the final stages of embryogenesis; ultimately, however, the elimination of the AS involves caspase-dependent nuclear fragmentation, tissue dissociation and engulfment by phagocytic macrophages. Mutants that are defective in the activation or execution of caspase-dependent PCD fail to degrade and eliminate the AS but show no abatement in AS autophagy. Sustained autophagy does not, therefore, necessarily result in cell death. Surprisingly, the downregulation of autophagy also results in a persistent AS phenotype and reduced cell death. Conversely, upregulation of autophagy results in caspase-dependent premature AS dissociation. These observations are consistent with the interpretation that autophagy is a prerequisite for caspase-dependent cell death in the AS.
自噬性细胞死亡与凋亡之间的关系是程序性细胞死亡（PCD）中一个尚未被充分理解的方面。我们通过研究果蝇发育过程中一种称为羊膜浆膜（AS）的胚外组织的清除来探讨这种关系。在胚胎发育的最后阶段，AS会发生自噬；然而，最终AS的清除涉及半胱天冬酶依赖性的核碎片化、组织解离以及被吞噬性巨噬细胞吞噬。在半胱天冬酶依赖性PCD的激活或执行方面存在缺陷的突变体无法降解和清除AS，但AS自噬并未减弱。因此，持续的自噬并不一定会导致细胞死亡。令人惊讶的是，自噬的下调也会导致AS持续存在的表型并减少细胞死亡。相反，自噬的上调会导致半胱天冬酶依赖性的AS过早解离。这些观察结果与自噬是AS中半胱天冬酶依赖性细胞死亡的先决条件这一解释一致。
