Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila
Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila
复制标题
DOI：
10.1016/j.cell.2007.10.048
复制
发表时间：
2007-12-14
期刊：
影响因子：
64.5
通讯作者：
Baehrecke, Eric H.
中科院分区：
文献类型：
--
作者：
Berry, Deborah L.;Baehrecke, Eric H.
自噬是一种受生长负调控的分解代谢过程，与细胞死亡有关。我们发现自噬在果蝇唾液腺生长停止后被诱导，并先于发育中的自噬细胞死亡。通过表达激活的Ras或I类磷酸肌醇3-激酶（PI3K）途径的正调节因子来维持生长，抑制自噬并阻止唾液腺细胞降解。在自噬基因（atg）突变体中唾液腺的发育退化也受到抑制。caspase在pi3k表达和atg突变的唾液腺中有活性，自噬和caspase的联合抑制增加了对腺体降解的抑制。此外，诱导自噬足以以不依赖于半胱天冬酶的方式诱导细胞过早死亡。我们的研究结果提供了体内证据，证明生长停滞、自噬和atg基因是生理自噬细胞死亡所必需的，并且多种降解途径在发育过程中协同有效地清除细胞。
Autophagy is a catabolic process that is negatively regulated by growth and has been implicated in cell death. We find that autophagy is induced following growth arrest and precedes developmental autophagic cell death of Drosophila salivary glands. Maintaining growth by expression of either activated Ras or positive regulators of the class I phosphoinositide 3-kinase (PI3K) pathway inhibits autophagy and blocks salivary gland cell degradation. Developmental degradation of salivary glands is also inhibited in autophagy gene (atg) mutants. Caspases are active in PI3K-expressing and atg mutant salivary glands, and combined inhibition of both autophagy and caspases increases suppression of gland degradation. Further, induction of autophagy is sufficient to induce premature cell death in a caspase-independent manner. Our results provide in vivo evidence that growth arrest, autophagy, and atg genes are required for physiological autophagic cell death and that multiple degradation pathways cooperate in the efficient clearance of cells during development.