Phosphatidylcholine deficiency increases ferroptosis susceptibility in the C. elegans germline.

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 (PUFAs), reactive oxygen species (ROS) , 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.

• Publication year

  2023

• Venue

  Journal of genetics and genomics = Yi chuan xue bao

• Publication date

  2023-03-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.jgg.2023.03.005PMID 36933794
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• OUP accepted manuscript

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