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Pink1/Parkin-Mediated Mitophagy Regulated the Apoptosis of Dendritic Cells in Sepsis

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Abstract

Dendritic cells (DCs) are vital antigen-presenting cells (APCs) in the immune system, whose apoptosis is closely related to the development of sepsis. Mitophagy is one of the necessary forms of selective autophagy that removes damaged or dysfunctional mitochondria to regulate immunity and inflammation. However, its effect on the apoptosis of DC in sepsis remains unknown. Here, we showed that sepsis activated the apoptosis and mitophagy of DC, and mitophagy had an anti-apoptotic effect on sepsis-induced DC apoptosis. In this study, we used cecal ligation and puncture (CLP) to simulate the pathophysiological state of sepsis. Apoptosis and mitophagy of DC were significantly enhanced in CLP mice compared with controls, and in the Pink1-KO (Pink1-knockout) mice CLP model, the level of apoptosis in DC was further increased while the level of mitophagy was decreased. In addition, more severe mitochondrial dysfunction was exhibited in DC of Pink1-KO mice CLP model compared to wild-type (WT) mice. The results suggest that Pink1/Parkin-mediated mitophagy is activated during sepsis and has an anti-apoptotic effect on DC, which regulates immune functions.

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Acknowledgements

We thank other members of our laboratories for helpful discussion and comments.

Funding

This work was supported by the National Natural Science Foundation of China (grant numbers 81772112).

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Author notes

  1. Yaolu Zhang, Longwang Chen, and Yinan Luo contributed equally.

Authors and Affiliations

  1. Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

    Yaolu Zhang, Longwang Chen, Yinan Luo, Kang Wang, Xinyong Liu, Zhong Xiao, Guangju Zhao & Zhongqiu Lu

  2. Key Laboratory of Emergency & Disaster Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

    Yaolu Zhang, Longwang Chen, Kang Wang, Xinyong Liu, Zhong Xiao, Guangju Zhao & Zhongqiu Lu

  3. Department of Critical Care Medicine, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Yinan Luo

  4. Trauma Research Center, Fourth Medical of the Chinese PLA General Hospital, Beijing, China

    Yongming Yao

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  1. Yaolu Zhang
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Contributions

Yaolu Zhang, Longwang Chen, and Yinan Luo contributed equally to this work. Yinan Luo, Yongming Yao, and Zhongqiu Lu designed the research. Yaolu Zhang, Longwang Chen, Yinan Luo, Kang Wang, Xinyong Liu, and Zhong Xiao performed the research. Yaolu Zhang, Longwang Chen, Yinan Luo, Kang Wang, Xinyong Liu, Zhong Xiao, and Guangju Zhao analyzed the data. Longwang Chen and Guangju Zhao contributed reagents. Yaolu Zhang and Longwang Chen wrote the paper.

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Correspondence to Yongming Yao or Zhongqiu Lu.

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All studies were performed according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and all methods were authorized by the ethics committee of the Laboratory Animal Ethics Committee of Wenzhou Medical University.

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Zhang, Y., Chen, L., Luo, Y. et al. Pink1/Parkin-Mediated Mitophagy Regulated the Apoptosis of Dendritic Cells in Sepsis. Inflammation 45, 1374–1387 (2022). https://doi.org/10.1007/s10753-022-01628-x

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  • DOI: https://doi.org/10.1007/s10753-022-01628-x

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