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An iron-dependent form of non-canonical ferroptosis induced by labile iron

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Abstract

Ferroptosis is a recently identified iron-dependent form of nonapoptotic cell death characterized by reactive oxygen species (ROS) generation and lipid peroxidation. Here, we report a novel iron-dependent form of ferroptosis induced by labile iron and investigate the mechanism underlying this process. We find that labile iron-induced ferroptosis is distinct from canonical ferroptosis and is linked to the mitochondrial pathway. Specifically, the mitochondrial calcium uniporter mediates the ferroptosis induced by labile iron. Interestingly, cells undergoing labile iron-induced ferroptosis exhibit cytoplasmic features of oncosis and nuclear features of apoptosis. Furthermore, labile iron-induced ferroptosis involves a unique set of genes. Finally, labile iron-induced ferroptosis was observed in liver subjected to acute iron overload in vivo. Our study reveals a novel form of ferroptosis that may be implicated in diseases caused by acute injury.

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Acknowledgements

This work was supported by the Beijing Natural Science Foundation (7202034) and the National Natural Science Foundation of China (82170614).

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Authors and Affiliations

  1. Beijing Clinical Research Institute, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China

    Yanmeng Li, Qin Ouyang, Wei Chen, Bei Zhang, Jingyi Yao, Song Zhang & Anjian Xu

  2. Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China

    Ke Liu & Junying Ding

  3. Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China

    Min Cong

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  1. Yanmeng Li
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  2. Qin Ouyang
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  3. Wei Chen
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  4. Ke Liu
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  9. Min Cong
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Correspondence to Junying Ding, Min Cong or Anjian Xu.

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Li, Y., Ouyang, Q., Chen, W. et al. An iron-dependent form of non-canonical ferroptosis induced by labile iron. Sci. China Life Sci. 66, 516–527 (2023). https://doi.org/10.1007/s11427-022-2244-4

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  • DOI: https://doi.org/10.1007/s11427-022-2244-4

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