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

Authors
Park, AnnaKim, Kwang-eunPark, IsaacLee, Sang HeonPark, Kun-YoungJung, MinkyoLi, XiaoxuSleiman, Maroun BouLee, Su JeongKim, Dae-SooKim, JaehoonLim, Dae-SikWoo, Eui-JeonLee, Eun WooHan, Baek SooOh, Kyoung-JinLee, Sang ChulAuwerx, Johan문지영Rhee, Hyun-WooKim, Won KonBae, Kwang-HeeSuh, Jae Myoung
Issue Date
Jun-2023
Publisher
Nature Publishing Group
Citation
Nature Communications, v.14, no.1
Journal Title
Nature Communications
Volume
14
Number
1
URI
http://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/122
DOI
10.1038/s41467-023-39106-z
ISSN
2041-1723
Abstract
<jats:title>Abstract</jats:title><jats:p>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. <jats:italic>Letmd1</jats:italic> knockout male mice display aberrant BAT mitochondria and fail to carry out adaptive thermogenesis under cold stress. <jats:italic>Letmd1</jats:italic> knockout BAT is deficient in oxidative phosphorylation (OXPHOS) complex proteins and has impaired mitochondrial respiration. In addition, BAT-specific <jats:italic>Letmd1</jats:italic> deficient mice exhibit phenotypes identical to those observed in <jats:italic>Letmd1</jats:italic> 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.</jats:p>
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