Mitochondrial LETM1 drives ionic and molecular clock rhythms in circadian pacemaker neurons
Mitochondrial LETM1 drives ionic and molecular clock rhythms in circadian pacemaker neurons
复制标题
DOI：
10.1016/j.celrep.2022.110787
复制
发表时间：
2022-05-10
期刊：
影响因子：
8.8
通讯作者：
Ikeda，Masayuki
中科院分区：
文献类型：
--
作者：
Morioka，Eri;Kasuga，Yusuke;Ikeda，Masayuki
在昼夜节律起搏神经元中产生强离子振荡的机制正在研究中。在此，我们证明了线粒体阳离子逆向转运蛋白亮氨酸拉链-EF-手含跨膜蛋白1（LETM 1）在昼夜节律起搏神经元中的关键功能，该蛋白在果蝇中负责K+/H+交换，在哺乳动物中负责Ca 2 +/H+交换。在大鼠下丘脑视交叉上核（SCN）起搏神经元中，Letm 1基因敲低抑制了胞浆Ca 2+和Bmal 1转录的昼夜节律。线粒体Ca ~（2+）摄取高峰在白天晚些时候也观察到大鼠SCN神经元的胞质Ca ~（2+）光解后的升高。由于LETM 1的阳离子转运与线粒体能量合成相结合，我们建议LETM 1在无脊椎动物和脊椎动物的中央时钟系统中整合代谢，离子和分子时钟节律。
The mechanisms that generate robust ionic oscillation in circadian pacemaker neurons are under investigation. Here, we demonstrate critical functions of the mitochondrial cation antiporter leucine zipper-EF-hand-containing transmembrane protein 1 (LETM1), which exchanges K+/H+inDrosophilaand Ca2+/H+in mammals, in circadian pacemaker neurons.Letm1knockdown inDrosophilapacemaker neurons reduced circadian cytosolic H+rhythms and prolonged nuclear PERIOD/TIMELESS expression rhythms and locomotor activity rhythms. In rat pacemaker neurons in the hypothalamic suprachiasmatic nucleus (SCN), circadian rhythms in cytosolic Ca2+andBmal1transcription were dampened byLetm1knockdown. Mitochondrial Ca2+uptake peaks late during the day were also observed in rat SCN neurons following photolytic elevation of cytosolic Ca2+. Since cation transport by LETM1 is coupled to mitochondrial energy synthesis, we propose that LETM1 integrates metabolic, ionic, and molecular clock rhythms in the central clock system in both invertebrates and vertebrates.