Phosphatidylcholine deficiency increases ferroptosis susceptibility in the Caenorhabditis elegans germline  

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

机构地区：[1]State Key Laboratory of Molecular Developmental Biology,Institute of Genetics and Developmental Biology,Chinese Academy of Sciences,Beijing 100101,China [2]University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Journal of Genetics and Genomics》2023年第5期318-329,共12页遗传学报（英文版）

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

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.

关 键 词：PHOSPHATIDYLCHOLINE Ferroptosis SPIN-4 STERILITY LYSOSOME 

分 类 号：R346[医药卫生—基础医学]