Human cervical cancer oncogene (HCCR-1), also named as LETMD1, is a LETM-domain containing outer mitochondrial membrane protein which plays an important role in the carcinogenesis of cancers. Surprisingly, we found that loss of Letmd1 in mice leads to multiply severe abnormities, such as the brown adipose tissue (BAT) whitening, disruption of thermogenesis, cold-induced death, diet-induced obesity, hyperglycinemia and insulin resistance. Mechanistically, deletion of Letmd1 in BAT causes the reduction of mitochondrial calcium ion, which in turn results in the suppressed fission of mitochondria, and ultimately leads to the depletion of Ucp1-mediated BAT heat production. This study indicates that LETMD1 plays a crucial role in controlling BAT thermogenesis and energy homeostasis by regulating mitochondrial structures and functions, and also provides a novel insight for the clinical biomarker and therapeutical target of oncogene for the metabolic disorders.

中文翻译：

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Letmd1的缺失导致棕色脂肪组织中线粒体功能的破坏

人类子宫颈癌致癌基因（HCCR-1），也称为LETMD1，是含有LETM结构域的线粒体外膜蛋白，在癌症的致癌作用中起着重要的作用。出人意料的是，我们发现小鼠中Letmd1的丢失导致多种严重异常，例如棕色脂肪组织（BAT）变白，生热破坏，冷诱发的死亡，饮食诱发的肥胖，高血糖症和胰岛素抵抗。从机理上讲，BAT中Letmd1的缺失会导致线粒体钙离子的减少，进而导致线粒体裂变受到抑制，最终导致Ucp1介导的BAT热量产生减少。这项研究表明，LETMD1通过调节线粒体的结构和功能，在控制BAT生热和能量稳态中起着至关重要的作用，