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Mitochondrial dynamics govern whole-body regeneration through stem cell pluripotency and mitonuclear balance

Author

Listed:
  • Xue Pan

    (Zhejiang University
    Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University
    Westlake Institute for Advanced Study)

  • Yun Zhao

    (Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University
    Westlake Institute for Advanced Study
    Fudan University)

  • Yucong Li

    (Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University
    Westlake Institute for Advanced Study
    Fudan University)

  • Jiajia Chen

    (Zhejiang University
    Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University
    Westlake Institute for Advanced Study)

  • Wenya Zhang

    (Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University
    Westlake Institute for Advanced Study
    Fudan University)

  • Ling Yang

    (Westlake University)

  • Yuanyi Zhou Xiong

    (Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University
    Westlake Institute for Advanced Study
    Fudan University)

  • Yuqing Ying

    (Zhejiang University
    Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University
    Westlake Institute for Advanced Study)

  • Hao Xu

    (Zhejiang University
    Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University
    Westlake Institute for Advanced Study)

  • Yuhong Zhang

    (Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University
    Westlake Institute for Advanced Study)

  • Chong Gao

    (Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University
    Westlake Institute for Advanced Study)

  • Yuhan Sun

    (Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University)

  • Nan Li

    (Westlake University)

  • Liangyi Chen

    (Peking University
    Peking University
    Peking University
    PKU‐Nanjing Institute of Translational Medicine)

  • Zhixing Chen

    (Peking University
    Peking University)

  • Kai Lei

    (Westlake Laboratory of Life Sciences and Biomedicine
    Westlake University
    Westlake Institute for Advanced Study)

Abstract

Tissue regeneration is a complex process involving large changes in cell proliferation, fate determination, and differentiation. Mitochondrial dynamics and metabolism play a crucial role in development and wound repair, but their function in large-scale regeneration remains poorly understood. Planarians offer an excellent model to investigate this process due to their remarkable regenerative abilities. In this study, we examine mitochondrial dynamics during planarian regeneration. We find that knockdown of the mitochondrial fusion gene, opa1, impairs both tissue regeneration and stem cell pluripotency. Interestingly, the regeneration defects caused by opa1 knockdown are rescued by simultaneous knockdown of the mitochondrial fission gene, drp1, which partially restores mitochondrial dynamics. Furthermore, we discover that Mitolow stem cells exhibit an enrichment of pluripotency due to their fate choices at earlier stages. Transcriptomic analysis reveals the delicate mitonuclear balance in metabolism and mitochondrial proteins in regeneration, controlled by mitochondrial dynamics. These findings highlight the importance of maintaining mitochondrial dynamics in large-scale tissue regeneration and suggest the potential for manipulating these dynamics to enhance stem cell functionality and regenerative processes.

Suggested Citation

  • Xue Pan & Yun Zhao & Yucong Li & Jiajia Chen & Wenya Zhang & Ling Yang & Yuanyi Zhou Xiong & Yuqing Ying & Hao Xu & Yuhong Zhang & Chong Gao & Yuhan Sun & Nan Li & Liangyi Chen & Zhixing Chen & Kai Le, 2024. "Mitochondrial dynamics govern whole-body regeneration through stem cell pluripotency and mitonuclear balance," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54720-1
    DOI: 10.1038/s41467-024-54720-1
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    References listed on IDEAS

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