Conserved role of ENDOG in promoting autophagy
Conserved role of ENDOG in promoting autophagy
复制标题
ENDOG 在促进自噬中的保守作用
DOI：
10.1080/15548627.2021.1907513
复制
发表时间：
2021
期刊：
影响因子：
13.3
通讯作者：
Qinghua Zhou
中科院分区：
文献类型：
--
作者：
Jianshuang Li;Wenjun Wang;Qinghua Zhou
摘要 ENDOG（核酸内切酶 G）是一种线粒体核酸内切酶，已知参与细胞凋亡和父系线粒体消除。然而，ENDOG在调节巨自噬中的作用和潜在机制仍不清楚。我们最近报道了线粒体释放的 ENDOG 在饥饿期间促进自噬，通过在人类细胞系、小鼠、果蝇和线虫中进行实验，我们证明了这种现象在物种间进化上是保守的。这项研究表明，ENDOG 可以被 GSK3B 磷酸化，从而增强 ENDOG 与 YWHAG 之间的相互作用，并导致 YWHAG 释放 TSC2 和 PIK3C3，随后抑制 MTOR 通路并启动自噬。此外，ENDOG 的核酸内切酶活性对于激活 DNA 损伤反应并从而诱导自噬至关重要。因此，这项研究揭示了 ENDOG 作为自噬的重要调节因子的令人兴奋的新作用。
ABSTRACT ENDOG (endonuclease G), a mitochondrial endonuclease, is known to participate in apoptosis and paternal mitochondria elimination. However, the role and underlying mechanism of ENDOG in regulating macroautophagy remain unclear. We recently reported that ENDOG released from mitochondria promotes autophagy during starvation, which we demonstrated is evolutionarily conserved across species by performing experiments in human cell lines, mice, Drosophila, and C. elegans. This study demonstrates that ENDOG can be phosphorylated by GSK3B, which enhances the interaction between ENDOG with YWHAG and leads to the release of TSC2 and PIK3C3 from YWHAG, followed by MTOR pathway suppression and autophagy initiation. Additionally, the endonuclease activity of ENDOG is essential for activating the DNA damage response and thus inducing autophagy. Consequently, this study uncovered an exciting new role for ENDOG as a crucial regulator of autophagy.