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ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cell Death and Survival
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1554958
Omic AI reveals new autophagy regulators from the Atg1 interactome in Saccharomyces cerevisiae
Provisionally accepted
Yu Xue1*
Cheng Han1
Shanshan Fu1Dachao Tang1Yuting Chen2Dan Liu1Zihao Feng1Yujie Gou1Chi Zhang1Weizhi Zhang1Leming Xiao1Jiayi Zhang1
Cong Yi2
Di Peng1- 1Huazhong University of Science and Technology, Wuhan, Hubei, China
- 2Zhejiang University, Hangzhou, Zhejiang Province, China
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In Saccharomyces cerevisiae, Atg1 is a core autophagy-related (Atg) protein kinase (PK) in regulating macroautophagy/autophagy, by physically interacting with numerous other proteins, or by phosphorylating various substrates. It's unclear how many Atg1-interacting partners and substrates are also involved in regulating autophagy. Here, we conducted transcriptomic, proteomic and phosphoproteomic profiling of Atg1-dependent molecular landscapes during nitrogen starvationtriggered autophagy, and detected 244, 245 and 217 genes to be affected by ATG1 in the autophagic process at mRNA, protein, and phosphorylation levels, respectively. Based on the Atg1 interactome, we developed a novel artificial intelligence (AI) framework, inference of autophagy regulators from multi-omic data (iAMD), and predicted 12 Atg1-interacting partners and 17 substrates to be potentially functional in autophagy. Further experiments validated that Rgd1 and Whi5 are required for bulk autophagy, as well as physical interactions and co-localizations with Atg1 during autophagy. In particular, we demonstrated that 2 phosphorylation sites (p-sites), pS78 and pS149 of Whi5, are phosphorylated by Atg1 to regulate the formation of Atg1 puncta during autophagy initiation. A working model was illustrated to emphasize the importance of the Atg1-centered network in yeast autophagy. In addition, iAMD was extended to accurately predict Atg proteins and autophagy regulators from other PK interactomes, indicating a high transferability of the method. Taken together, we not only revealed new autophagy regulators from the Atg1 interactome, but also provided a useful resource for further analysis of yeast autophagy.
Keywords: Atg1, Autophagy-related, protein kinase, artificial intelligence, deep learning, Phosphorylation
Received: 03 Jan 2025; Accepted: 16 Apr 2025.
Copyright: © 2025 Xue, Han, Fu, Tang, Chen, Liu, Feng, Gou, Zhang, Zhang, Xiao, Zhang, Yi and Peng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yu Xue, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.