Abstract:
Mitochondrial function can be regulated by ion channels. Mitochondrial RNA splicing 2 (Mrs2) is a magnesium ion (Mg2+) channel located in the inner mitochondrial membrane, thereby mediating the Mg2+ influx into the mitochondrial matrix. However, its potential role in regulating the Mg homeostasis and mitochondrial function in aquatic species is still unclear. This study molecularly characterizes the gene encoding Mrs2 in fish M. amblycephala with its functions in maintaining the Mg homeostasis and mitochondrial function verified. The mrs2 gene is 2133 bp long incorporating a 1269 bp open reading frame, which encodes 422 amino acids. The Mrs2 protein includes two transmembrane domains and a conserved tripeptide Gly-Met-Asn, and has a high homology (65.92-97.64%) with those of most vertebrates. The transcript of mrs2 was relatively high in the white muscle, liver and kidney. The inhibition of mrs2 reduces the expressions of Mg2+ influx/efflux-related proteins, mitochondrial Mg content, and the activities of mitochondrial complex I and V in hepatocytes. However, the over-expression of mrs2 increases the expressions of Mg2+ influx/efflux-related proteins, mitochondrial Mg content, and the complex V activity, but decreases the activities of mitochondrial complex III and IV and citrate synthase in hepatocytes. Collectively, Mrs2 is highly conserved among different species, and is prerequisite for maintaining Mg homeostasis and mitochondrial function in fish.
摘要:
线粒体功能可以通过离子通道调节。线粒体RNA剪接2(Mrs2)是位于线粒体内膜的镁离子(Mg2+)通道,从而介导Mg2+流入线粒体基质。然而,其在调节水生物种Mg稳态和线粒体功能中的潜在作用尚不清楚。这项研究在分子上表征了鱼M中编码Mrs2的基因,并验证了其在维持Mg稳态和线粒体功能方面的功能。mrs2基因长2133bp,包含一个1269bp的开放阅读框,编码422个氨基酸。Mrs2蛋白包括两个跨膜结构域和一个保守的三肽Gly-Met-Asn,与大多数脊椎动物具有很高的同源性(65.92-97.64%)。mrs2的转录在白肌中相对较高,肝脏和肾脏。mrs2的抑制降低了Mg2+内流/外流相关蛋白的表达,线粒体Mg含量,以及肝细胞中线粒体复合物I和V的活性。然而,mrs2的过表达增加了Mg2+流入/流出相关蛋白的表达,线粒体Mg含量,和复杂的V活性,但降低肝细胞中线粒体复合物III和IV以及柠檬酸合酶的活性。总的来说,Mrs2在不同物种之间高度保守,是维持鱼类镁稳态和线粒体功能的前提。