Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai, Guangdong, China.
Autophagy. 2021 Apr;17(4):1061-1062. doi: 10.1080/15548627.2021.1907513. Epub 2021 Mar 28.
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, , and . 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.
ENDOG（endonuclease G）是一种线粒体内切核酸酶，已知它参与细胞凋亡和父系线粒体的消除。然而，ENDOG 在调节巨自噬中的作用和潜在机制尚不清楚。我们最近报道，从线粒体中释放的 ENDOG 在饥饿期间促进自噬，我们通过在人细胞系、小鼠、 和 中进行实验证明了这一过程在物种间是保守的。这项研究表明，ENDOG 可以被 GSK3B 磷酸化，这增强了 ENDOG 与 YWHAG 的相互作用，导致 TSC2 和 PIK3C3 从 YWHAG 中释放，从而抑制 MTOR 通路并启动自噬。此外，ENDOG 的内切核酸酶活性对于激活 DNA 损伤反应从而诱导自噬是必不可少的。因此，这项研究揭示了 ENDOG 作为自噬关键调节剂的令人兴奋的新作用。
