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

Bibliographic Details
Title: Mitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice
Authors: 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 Lee, Baek Soo Han, Kyoung-Jin Oh, Sang Chul Lee, Johan Auwerx, Ji Young Mun, Hyun-Woo Rhee, Won Kon Kim, Kwang-Hee Bae, Jae Myoung Suh
Source: Nature Communications, Vol 14, Iss 1, Pp 1-14 (2023)
Publisher Information: Nature Portfolio, 2023.
Publication Year: 2023
Collection: LCC:Science
Subject Terms: Science
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2041-1723
Relation: https://doaj.org/toc/2041-1723
DOI: 10.1038/s41467-023-39106-z
Access URL: https://doaj.org/article/8abfab449c994b11bb6233d6bda9aba7
Accession Number: edsdoj.8abfab449c994b11bb6233d6bda9aba7
Database: Directory of Open Access Journals
More Details
ISSN:20411723
DOI:10.1038/s41467-023-39106-z
Published in:Nature Communications
Language:English