Phosphatidylcholine deficiency increases ferroptosis susceptibility in the Caenorhabditis elegans germline

作     者：Jinglin Zhu Wei Meng Sin Man Lam Guanghou Shui Xun Huang Jinglin Zhu;Wei Meng;Sin Man Lam;Guanghou Shui;Xun Huang

作者机构：State Key Laboratory of Molecular Developmental BiologyInstitute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of SciencesBeijing 100049China 

出 版 物：《Journal of Genetics and Genomics》 (遗传学报（英文版）)

年 卷 期：2023年第50卷第5期

页      面：318-329页

核心收录：

学科分类：0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China and the Ministry of Science and Technology of China (32230044  91954207  and 2018YFA0506902) 

主　　题：Phosphatidylcholine Ferroptosis SPIN-4 Sterility Lysosome 

摘      要：Ferroptosis,a regulated and iron-dependent form of cell death characterized by peroxidation of membrane phospholipids,has tremendous potential for the therapy of human diseases.The causal link between phospholipid homeostasis and ferroptosis is incompletely understood.Here,we reveal that spin-4,a previously identified regulator of the“B12-one-carbon cycle-phosphatidylcholine(PC)pathway,sustains germline development and fertility by ensuring PC sufficiency in the nematode Caenorhabditis elegans.Mechanistically,SPIN-4 regulates lysosomal activity which is required for B12-associated PC synthesis.PC deficiency-induced sterility can be rescued by reducing the levels of polyunsaturated fatty acids,reactive oxygen species,and redox-active iron,which indicates that the sterility is mediated by germline ferroptosis.These results highlight the critical role of PC homeostasis in ferroptosis susceptibility and offer a new target for pharmacological approaches.