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

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...

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Autores principales: Park, Anna, Kim, Kwang-eun, Park, Isaac, Lee, Sang Heon, Park, Kun-Young, Jung, Minkyo, Li, Xiaoxu, Sleiman, Maroun Bou, Lee, Su Jeong, Kim, Dae-Soo, Kim, Jaehoon, Lim, Dae-Sik, Woo, Eui-Jeon, Lee, Eun Woo, Han, Baek Soo, Oh, Kyoung-Jin, Lee, Sang Chul, Auwerx, Johan, Mun, Ji Young, Rhee, Hyun-Woo, Kim, Won Kon, Bae, Kwang-Hee, Suh, Jae Myoung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10290150/
https://www.ncbi.nlm.nih.gov/pubmed/37353518
http://dx.doi.org/10.1038/s41467-023-39106-z
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author Park, Anna
Kim, Kwang-eun
Park, Isaac
Lee, Sang Heon
Park, Kun-Young
Jung, Minkyo
Li, Xiaoxu
Sleiman, Maroun Bou
Lee, Su Jeong
Kim, Dae-Soo
Kim, Jaehoon
Lim, Dae-Sik
Woo, Eui-Jeon
Lee, Eun Woo
Han, Baek Soo
Oh, Kyoung-Jin
Lee, Sang Chul
Auwerx, Johan
Mun, Ji Young
Rhee, Hyun-Woo
Kim, Won Kon
Bae, Kwang-Hee
Suh, Jae Myoung
author_facet Park, Anna
Kim, Kwang-eun
Park, Isaac
Lee, Sang Heon
Park, Kun-Young
Jung, Minkyo
Li, Xiaoxu
Sleiman, Maroun Bou
Lee, Su Jeong
Kim, Dae-Soo
Kim, Jaehoon
Lim, Dae-Sik
Woo, Eui-Jeon
Lee, Eun Woo
Han, Baek Soo
Oh, Kyoung-Jin
Lee, Sang Chul
Auwerx, Johan
Mun, Ji Young
Rhee, Hyun-Woo
Kim, Won Kon
Bae, Kwang-Hee
Suh, Jae Myoung
author_sort Park, Anna
collection PubMed
description 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.
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spelling pubmed-102901502023-06-25 Mitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice Park, Anna Kim, Kwang-eun Park, Isaac Lee, Sang Heon Park, Kun-Young Jung, Minkyo Li, Xiaoxu Sleiman, Maroun Bou Lee, Su Jeong Kim, Dae-Soo Kim, Jaehoon Lim, Dae-Sik Woo, Eui-Jeon Lee, Eun Woo Han, Baek Soo Oh, Kyoung-Jin Lee, Sang Chul Auwerx, Johan Mun, Ji Young Rhee, Hyun-Woo Kim, Won Kon Bae, Kwang-Hee Suh, Jae Myoung Nat Commun Article 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. Nature Publishing Group UK 2023-06-23 /pmc/articles/PMC10290150/ /pubmed/37353518 http://dx.doi.org/10.1038/s41467-023-39106-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Park, Anna
Kim, Kwang-eun
Park, Isaac
Lee, Sang Heon
Park, Kun-Young
Jung, Minkyo
Li, Xiaoxu
Sleiman, Maroun Bou
Lee, Su Jeong
Kim, Dae-Soo
Kim, Jaehoon
Lim, Dae-Sik
Woo, Eui-Jeon
Lee, Eun Woo
Han, Baek Soo
Oh, Kyoung-Jin
Lee, Sang Chul
Auwerx, Johan
Mun, Ji Young
Rhee, Hyun-Woo
Kim, Won Kon
Bae, Kwang-Hee
Suh, Jae Myoung
Mitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice
title Mitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice
title_full Mitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice
title_fullStr Mitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice
title_full_unstemmed Mitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice
title_short Mitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice
title_sort mitochondrial matrix protein letmd1 maintains thermogenic capacity of brown adipose tissue in male mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10290150/
https://www.ncbi.nlm.nih.gov/pubmed/37353518
http://dx.doi.org/10.1038/s41467-023-39106-z
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