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Nuclear localization of mitochondrial TCA cycle enzymes modulates pluripotency via histone acetylation

Author

Listed:
  • Wei Li

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Qi Long

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences)

  • Hao Wu

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences)

  • Yanshuang Zhou

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences)

  • Lifan Duan

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Hao Yuan

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences)

  • Yingzhe Ding

    (Chinese Academy of Sciences)

  • Yile Huang

    (Chinese Academy of Sciences)

  • Yi Wu

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences)

  • Jinyu Huang

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences)

  • Delong Liu

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences)

  • Baodan Chen

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences)

  • Jian Zhang

    (Chinese Academy of Sciences; Guangzhou Medical University)

  • Juntao Qi

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Shiwei Du

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Linpeng Li

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences)

  • Yang Liu

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Zifeng Ruan

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Zihuang Liu

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Zichao Liu

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yifan Zhao

    (Chinese Academy of Sciences)

  • Jianghuan Lu

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences)

  • Junwei Wang

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences)

  • Wai-Yee Chan

    (The Chinese University of Hong Kong)

  • Xingguo Liu

    (Chinese Academy of Sciences; Guangzhou Medical University
    Chinese Academy of Sciences
    Chinese Academy of Sciences)

Abstract

Pluripotent stem cells hold great promise in regenerative medicine and developmental biology studies. Mitochondrial metabolites, including tricarboxylic acid (TCA) cycle intermediates, have been reported to play critical roles in pluripotency. Here we show that TCA cycle enzymes including Pdha1, Pcb, Aco2, Cs, Idh3a, Ogdh, Sdha and Mdh2 are translocated to the nucleus during somatic cell reprogramming, primed-to-naive transition and totipotency acquisition. The nuclear-localized TCA cycle enzymes Pdha1, Pcb, Aco2, Cs, Idh3a promote somatic cell reprogramming and primed-to-naive transition. In addition, nuclear-localized TCA cycle enzymes, particularly nuclear-targeted Pdha1, facilitate the 2-cell program in pluripotent stem cells. Mechanistically, nuclear Pdha1 increases the acetyl-CoA and metabolite pool in the nucleus, leading to chromatin remodeling at pluripotency genes by enhancing histone H3 acetylation. Our results reveal an important role of mitochondrial TCA cycle enzymes in the epigenetic regulation of pluripotency that constitutes a mitochondria-to-nucleus retrograde signaling mode in different states of pluripotent acquisition.

Suggested Citation

  • Wei Li & Qi Long & Hao Wu & Yanshuang Zhou & Lifan Duan & Hao Yuan & Yingzhe Ding & Yile Huang & Yi Wu & Jinyu Huang & Delong Liu & Baodan Chen & Jian Zhang & Juntao Qi & Shiwei Du & Linpeng Li & Yang, 2022. "Nuclear localization of mitochondrial TCA cycle enzymes modulates pluripotency via histone acetylation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35199-0
    DOI: 10.1038/s41467-022-35199-0
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    References listed on IDEAS

    as
    1. Radhika Puttagunta & Andrea Tedeschi & Marilia Grando Sória & Arnau Hervera & Ricco Lindner & Khizr I. Rathore & Perrine Gaub & Yashashree Joshi & Tuan Nguyen & Antonio Schmandke & Claudia J. Laskowsk, 2014. "PCAF-dependent epigenetic changes promote axonal regeneration in the central nervous system," Nature Communications, Nature, vol. 5(1), pages 1-13, May.
    2. Shinya Yamanaka & Helen M. Blau, 2010. "Nuclear reprogramming to a pluripotent state by three approaches," Nature, Nature, vol. 465(7299), pages 704-712, June.
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    Cited by:

    1. Fabiola Diniz & Nguyen Yen Nhi Ngo & Mariel Colon-Leyva & Francesca Edgington-Giordano & Sylvia Hilliard & Kevin Zwezdaryk & Jiao Liu & Samir S. El-Dahr & Giovane G. Tortelote, 2023. "Acetyl-CoA is a key molecule for nephron progenitor cell pool maintenance," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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