한빛사논문
- 조회601
Anna Park1,14, Kwang-eun Kim2,3,14, Isaac Park3, Sang Heon Lee2, Kun-Young Park 2, Minkyo Jung4, Xiaoxu Li5, Maroun Bou Sleiman5, Su Jeong Lee1,6, Dae-Soo Kim6,7, Jaehoon Kim8, Dae-Sik Lim9, Eui-Jeon Woo6,10, Eun Woo Lee1,6, Baek Soo Han6,11, Kyoung-Jin Oh1,6, Sang Chul Lee1, Johan Auwerx5, Ji Young Mun4, Hyun-Woo Rhee3, Won Kon Kim1,6,12 , Kwang-Hee Bae1,13 & Jae Myoung Suh2
1Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
2Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Republic of Korea.
3Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea.
4Neural Circuit Research Group, Korea Brain Research Institute, Daegu 41068, Republic of Korea.
5Laboratory of Integrative Systems Physiology, École polytechnique fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
6Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon 34141, Republic of Korea.
7Digital Biotech Innovation Center, KRIBB, Daejeon 34141, Republic of Korea.
8Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea.
9National Creative Research Center for Cell Plasticity, KAIST Stem Cell Center, Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea.
10Disease Target Structure Research Center, KRIBB, Daejeon 34141, Republic of Korea.
11Biodefense Research Center, KRIBB, Daejeon 34141, Republic of Korea.
12School of Medicine, Sungkyunkwan University, Suwon 16419, Republic of Korea.
13Department of Developmental and Cell Biology, School of Biological Sciences, University of California, Irvine, CA 92697, USA.
14These authors contributed equally: Anna Park, Kwang-eun Kim.
Corresponding authors : Correspondence to Won Kon Kim, Kwang-Hee Bae or Jae Myoung Suh.
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.
논문정보
- Research article
- 2023년 06월 (BRIC 등록일 2023-06-26)
- 국내(교신)+국외 연구진
- 의약학 > 분자세포의학
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