Nezis Ioannis P, Lamark Trond, Velentzas Athanassios D, Rusten Tor Erik, Bjørkøy Geir, Johansen Terje, Papassideri Issidora S, Stravopodis Dimitrios J, Margaritis Lukas H, Stenmark Harald, Brech Andreas
Centre for Cancer Biomedicine, University of Oslo and Institute for Cancer Research, Department of Biochemistry, Rikshospitalet-Radiumhospitalet HF, Montebello, Oslo, Norway.
Autophagy. 2009 Apr;5(3):298-302. doi: 10.4161/auto.5.3.7454. Epub 2009 Apr 19.
Autophagy is a physiological and evolutionarily conserved process maintaining homeostatic functions, such as protein degradation and organelle turnover. Accumulating data provide evidence that autophagy also contributes to cell death under certain circumstances, but how this is achieved is not well known. Herein, we report that autophagy occurs during developmentally-induced cell death in the female germline, observed in the germarium and during middle developmental stages of oogenesis in Drosophila melanogaster. Degenerating germline cells exhibit caspase activation, chromatin condensation, DNA fragmentation and punctate staining of mCherry-DrAtg8a, a novel marker for monitoring autophagy in Drosophila. Genetic inhibition of autophagy, by removing atg1 or atg7 function, results in significant reduction of DNA fragmentation, suggesting that autophagy acts genetically upstream of DNA fragmentation in this tissue. This study provides new insights into the mechanisms that regulate cell death in vivo during development.
自噬是一种生理上保守且进化上保守的过程,维持着诸如蛋白质降解和细胞器更新等稳态功能。越来越多的数据表明,自噬在某些情况下也会导致细胞死亡,但具体实现方式尚不清楚。在此,我们报告自噬发生在雌性生殖系发育诱导的细胞死亡过程中,在果蝇的卵巢小管以及卵子发生的中期发育阶段均可观察到。退化的生殖系细胞表现出半胱天冬酶激活、染色质浓缩、DNA片段化以及mCherry-DrAtg8a的点状染色,mCherry-DrAtg8a是果蝇中监测自噬的一种新型标记物。通过去除atg1或atg7功能对自噬进行基因抑制,会导致DNA片段化显著减少,这表明在该组织中自噬在基因上作用于DNA片段化的上游。这项研究为发育过程中体内调节细胞死亡的机制提供了新的见解。