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Mitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice

Author

Listed:
  • Anna Park

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Kwang-eun Kim

    (KAIST
    Seoul National University)

  • Isaac Park

    (Seoul National University)

  • Sang Heon Lee

    (KAIST)

  • Kun-Young Park

    (KAIST)

  • Minkyo Jung

    (Korea Brain Research Institute)

  • Xiaoxu Li

    (École polytechnique fédérale de Lausanne (EPFL))

  • Maroun Bou Sleiman

    (École polytechnique fédérale de Lausanne (EPFL))

  • Su Jeong Lee

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Dae-Soo Kim

    (Korea University of Science and Technology (UST)
    Digital Biotech Innovation Center, KRIBB)

  • Jaehoon Kim

    (KAIST)

  • Dae-Sik Lim

    (KAIST)

  • Eui-Jeon Woo

    (Korea University of Science and Technology (UST)
    KRIBB)

  • Eun Woo Lee

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Baek Soo Han

    (Korea University of Science and Technology (UST)
    Biodefense Research Center, KRIBB)

  • Kyoung-Jin Oh

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Sang Chul Lee

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Johan Auwerx

    (École polytechnique fédérale de Lausanne (EPFL))

  • Ji Young Mun

    (Korea Brain Research Institute)

  • Hyun-Woo Rhee

    (Seoul National University)

  • Won Kon Kim

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST)
    Sungkyunkwan University)

  • Kwang-Hee Bae

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    University of California)

  • Jae Myoung Suh

    (KAIST)

Abstract

Brown adipose tissue (BAT) has abundant mitochondria with the unique capability of generating heat via uncoupled respiration. Mitochondrial uncoupling protein 1 (UCP1) is activated in BAT during cold stress and dissipates mitochondrial proton motive force generated by the electron transport chain to generate heat. However, other mitochondrial factors required for brown adipocyte respiration and thermogenesis under cold stress are largely unknown. Here, we show LETM1 domain-containing protein 1 (LETMD1) is a BAT-enriched and cold-induced protein required for cold-stimulated respiration and thermogenesis of BAT. Proximity labeling studies reveal that LETMD1 is a mitochondrial matrix protein. Letmd1 knockout male mice display aberrant BAT mitochondria and fail to carry out adaptive thermogenesis under cold stress. Letmd1 knockout BAT is deficient in oxidative phosphorylation (OXPHOS) complex proteins and has impaired mitochondrial respiration. In addition, BAT-specific Letmd1 deficient mice exhibit phenotypes identical to those observed in Letmd1 knockout mice. Collectively, we demonstrate that the BAT-enriched mitochondrial matrix protein LETMD1 plays a tissue-autonomous role that is essential for BAT mitochondrial function and thermogenesis.

Suggested Citation

  • Anna Park & Kwang-eun Kim & Isaac Park & Sang Heon Lee & Kun-Young Park & Minkyo Jung & Xiaoxu Li & Maroun Bou Sleiman & Su Jeong Lee & Dae-Soo Kim & Jaehoon Kim & Dae-Sik Lim & Eui-Jeon Woo & Eun Woo, 2023. "Mitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39106-z
    DOI: 10.1038/s41467-023-39106-z
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