所在院系：基础医学院

申报人：易聪

蛋白质聚集是多种人类疾病的标志。选择性自噬在降解蛋白质聚集体过程中发挥重要作用。然而，如何实现选择性降解聚集体并不十分清楚。我们与清华大学团队合作发现一种新型的聚集体自噬受体CCT2，在降解固态蛋白质聚集体过程中发挥重要作用（Cell）。我们也发现选择性自噬标志蛋白Atg11可以被蛋白激酶Atg1磷酸化修饰，进而促进选择性自噬受体与Atg11的结合进而启动自噬发生（Autophagy）。同时，我们发现一种新型的细胞器互作，介导了能量匮乏诱导自噬的发生（PNAS）。

Protein aggregation is a hallmark of multiple human pathologies. Selective autophagy plays a crucial role in the degradation of protein aggregates. However, how selectivity is achieved has been elusive. We collaborated with a team from Tsinghua University to discover a novel aggrephagy receptor CCT2, which specifically promotes the autophagic degradation of protein aggregates with liquidity (Cell). We also found that the selective autophagy marker protein Atg11 can be phosphorylated by the protein kinase Atg1, thereby promoting the binding of selective autophagy receptors to Atg11 and initiating autophagy. Concurrently, we found a novel organelle contact that mediates energy deprivation-induced autophagy (PNAS).

图1易聪照片

图2新型选择性自噬受体CCT2降解固态蛋白聚集体的工作模式图（Cell）

图3Atg1磷酸化Atg11促进选择性自噬受体与Atg11互作的工作模式图（Autophagy）

图4线粒体和自噬体互作启动能量匮乏诱导自噬的工作模式图（PNAS）

1. Weijing Yao^#, Yixing Li^#, Yingcong Chen^#, Yuting Chen^#, Pengwei Zhao, Yi Zhang, Qiang Jiang, Yuyao Feng, Fan Yang, Choufei Wu, Huiming Zhong, Yiting Zhou, Qiming Sun, Liqin Zhang, Wei Liu, Cong Yi*. Mec1 regulates PAS recruitment of Atg13 via direct binding with Atg13 during glucose starvation- induced autophagy. PNAS. 2023 Jan 3;120(1):e2215126120. Epub 2022 Dec 27.

2. Weijing Yao^#, Yixing Li^#, Yingcong Chen^#, Yuting Chen^#, Yu Xie, Miaojuan Ye, Ying Zhang, Xiangjun Chen, Xiaoyong Wu, Yuyao Feng, Zhi Hong, Yigang Wang, Wei Liu, Cong Yi*. Atg1-mediated Atg11 phosphorylation is required for selective autophagy by regulating its association with receptor proteins. Autophagy. 2023 Jan;19(1):180-188. Epub 2022 Apr 15.

3.Xinyu Ma, Caijing Lu, Yuting Chen, Shulin Li, Ningjia Ma, Xuan Tao, Ying Li, Jing Wang, Min Zhou, Yong-Bin Yan, Pilong Li, Kartoosh Heydari, Haiteng Deng, Min Zhang*, Cong Yi*, Liang Ge*. CCT2 is an aggrephagy receptor for clearance of solid protein aggregates. Cell. 2022 Apr 14;185(8):1325-1345.e22. Epub 2022 Apr 1.