Mitochondria-localized circRNA BRAKE restrains adipogenesis under nutrient overload by disrupting ATP synthase assembly in mice
Abstract
Impaired adipogenesis contributes to obesity-associated metabolic disorders, in which mitochondrial dysfunction plays an important role. Emerging evidence suggests that mitochondria-localized circular RNAs (circRNAs) influence mitochondrial function; however, whether they regulate adipogenesis and systemic metabolism is unclear. By profiling circRNAs in mitochondria isolated from the white adipose tissue (WAT) of obese male mice, we observe an upregulation of Birc6 -circRNA Repressing Adipogenesis and Krebs-cycle Energy (BRAKE) in mitochondria. In vivo, adipocyte-specific circRNA BRAKE knockdown in male mice reduces body weight, restricts fat expansion, and improves insulin sensitivity. In vitro studies show that circRNA BRAKE inhibits adipogenesis. Mechanistically, circRNA BRAKE binds ATP5A and disrupts ATP synthase assembly, thereby reducing ATP production and mTORC1 signaling and suppressing adipogenesis. In omental WAT (oWAT) of patients with obesity, mitochondrial circRNA BRAKE levels are elevated and inversely correlated with mitochondrial bioenergetic function. Collectively, our data identify a mitochondria-localized circRNA that regulates energy metabolism and adipogenesis, suggesting that circRNA BRAKE may represent a potential therapeutic target for obesity-related metabolic diseases.
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BibTeX
@article{huang2026mitochondrialocalized,
title = {{Mitochondria-localized circRNA BRAKE restrains adipogenesis under nutrient overload by disrupting ATP synthase assembly in mice}},
author = {Yanrui Huang and Tianxin Zhu and Xiaosi Hong and Yulin Yang and Jianyou Liao and Jiayu Liu and Chunni Li and Wei Wang and Sifan Chen and Phei Er Saw and Yanbing Li and Haipeng Xiao and Meng Ren and Shicheng Su and Yanrui Huang},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78378-z},
url = {https://www.nature.com/articles/s41467-026-78378-z},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mitochondria-localized circRNA BRAKE restrains adipogenesis under nutrient overload by disrupting ATP synthase assembly in mice
AU - Yanrui Huang
AU - Tianxin Zhu
AU - Xiaosi Hong
AU - Yulin Yang
AU - Jianyou Liao
AU - Jiayu Liu
AU - Chunni Li
AU - Wei Wang
AU - Sifan Chen
AU - Phei Er Saw
AU - Yanbing Li
AU - Haipeng Xiao
AU - Meng Ren
AU - Shicheng Su
AU - Yanrui Huang
PY - 2026
DA - 2026/10/13
JO - Nature Communications
DO - 10.1038/s41467-026-78378-z
UR - https://www.nature.com/articles/s41467-026-78378-z
AB - Impaired adipogenesis contributes to obesity-associated metabolic disorders, in which mitochondrial dysfunction plays an important role. Emerging evidence suggests that mitochondria-localized circular RNAs (circRNAs) influence mitochondrial function; however, whether they regulate adipogenesis and systemic metabolism is unclear. By profiling circRNAs in mitochondria isolated from the white adipose tissue (WAT) of obese male mice, we observe an upregulation of Birc6 -circRNA Repressing Adipogenesis and Krebs-cycle Energy (BRAKE) in mitochondria. In vivo, adipocyte-specific circRNA BRAKE knockdown in male mice reduces body weight, restricts fat expansion, and improves insulin sensitivity. In vitro studies show that circRNA BRAKE inhibits adipogenesis. Mechanistically, circRNA BRAKE binds ATP5A and disrupts ATP synthase assembly, thereby reducing ATP production and mTORC1 signaling and suppressing adipogenesis. In omental WAT (oWAT) of patients with obesity, mitochondrial circRNA BRAKE levels are elevated and inversely correlated with mitochondrial bioenergetic function. Collectively, our data identify a mitochondria-localized circRNA that regulates energy metabolism and adipogenesis, suggesting that circRNA BRAKE may represent a potential therapeutic target for obesity-related metabolic diseases.
SN - 2041-1723
ER -