The lncRNA HOXA11os regulates mitochondrial function in myeloid cells to maintain intestinal homeostasis.
The lncRNA HOXA11os regulates mitochondrial function in myeloid cells to maintain intestinal homeostasis.
复制标题
lncRNA HOXA11os 调节骨髓细胞中的线粒体功能以维持肠道稳态。
DOI：
10.1016/j.cmet.2023.06.019
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发表时间：
2023
期刊：
影响因子：
29
通讯作者：
Henao-Mejia,
中科院分区：
文献类型：
--
作者：
Shmuel-Galia,Liraz;Humphries,Fiachra;Vierbuchen,Tim;Jiang,Zhaozhao;Santos,Nolan;Johnson,John;Shklyar,Boris;Joannas,Leonel;Mustone,Nicholas;Sherman,Shany;Ward,Doyle;Houghton,JeanMarie;Baer,ChristinaE;O'Hara,Aisling;Henao-Mejia,
This study reveals a previously uncharacterized mechanism to restrict intestinal inflammation via a regulatory RNA transcribed from a noncoding genomic locus. We identified a novel transcript of the lncRNA HOXA11os specifically expressed in the distal colon that is reduced to undetectable levels in colitis. HOXA11os is localized to mitochondria under basal conditions and interacts with a core subunit of complex 1 of the electron transport chain (ETC) to maintain its activity. Deficiency of HOXA11os in colonic myeloid cells results in complex I deficiency, dysfunctional oxidative phosphorylation (OXPHOS), and the production of mitochondrial reactive oxygen species (mtROS). As a result, HOXA11os-deficient mice develop spontaneous intestinal inflammation and are hypersusceptible to colitis. Collectively, these studies identify a new regulatory axis whereby a lncRNA maintains intestinal homeostasis and restricts inflammation in the colon through the regulation of complex I activity.
