Phosphatidylcholine deficiency increases ferroptosis susceptibility in the <i>Caenorhabditis elegans</i> germline

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

doi:10.1016/j.jgg.2023.03.005

Volume 50 Issue 5

May 2023

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Article Navigation > Journal of Genetics and Genomics > 2023 > 50(5): 318-329

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Phosphatidylcholine deficiency increases ferroptosis susceptibility in the Caenorhabditis elegans germline

doi: 10.1016/j.jgg.2023.03.005

a. State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;
b. University of Chinese Academy of Sciences, Beijing 100049, China

Funds:

We thank Dr. Xiaochen Wang, Dr. Jingyan Zhang, Dr. Bin Liang, and the Caenorhabditis Genetics Center (CGC) for providing C. elegans strains. This research was supported by the National Natural Science Foundation of China and the Ministry of Science and Technology of China (32230044, 91954207, and 2018YFA0506902).

Received Date: 2022-09-28
Accepted Date: 2023-03-06
Rev Recd Date: 2023-02-15
Publish Date: 2023-03-16

Abstract

Abstract

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.
- Phosphatidylcholine,
- Ferroptosis,
- SPIN-4,
- Sterility,
- Lysosome

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References(57)

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