Phosphatidylserine transport by Ups2-Mdm35 in respiration-active mitochondria.
Phosphatidylserine transport by Ups2-Mdm35 in respiration-active mitochondria.
复制标题
DOI：
10.1083/jcb.201601082
复制
发表时间：
2016-07-04
期刊：
影响因子：
--
通讯作者：
Kuge O
中科院分区：
文献类型：
--
作者：
Miyata N;Watanabe Y;Tamura Y;Endo T;Kuge O
磷脂酰乙醇胺是线粒体功能必需的磷脂，在线粒体内膜合成。Miyata等人证明，线粒体膜间空间的蛋白复合物Ups2-Mdm35在酿酒酵母呼吸活性线粒体中介导磷脂酰丝氨酸转运，用于合成磷脂酰乙醇胺。磷脂酰乙醇胺（PE）是线粒体功能必需的磷脂，主要由线粒体内膜上的磷脂酰丝氨酸（PS）脱羧酶合成。在酿酒酵母中，PS是在内质网（ER）中合成的，因此线粒体PE的合成需要PS从内质网转运到线粒体内膜。在这里，我们提供的证据表明，Ups2-Mdm35是一种定位于线粒体膜间隙的蛋白质复合物，在呼吸活性线粒体中介导PS运输以合成PE。UPS2-和MDM35-null突变极大地减弱了在不可发酵条件下生长的酵母细胞中PS向PE的转化，而不是在可发酵条件下。重组Ups2-Mdm35融合蛋白在体外脂质体之间表现出磷脂转移活性。此外，在非发酵条件下和在双氧转换（从糖酵解到氧化磷酸化的代谢转变）时，UPS2表达升高。这些结果表明，Ups2-Mdm35作为PS转移蛋白，在细胞代谢状态下促进线粒体PE合成。
Phosphatidylethanolamine, an essential phospholipid for mitochondrial functions, is synthesized at the mitochondrial inner membrane. Miyata et al. demonstrate that Ups2–Mdm35, a protein complex in the mitochondrial intermembrane space, mediates phosphatidylserine transport for phosphatidylethanolamine synthesis in respiration-active mitochondria of Saccharomyces cerevisiae. Phosphatidylethanolamine (PE) is an essential phospholipid for mitochondrial functions and is synthesized mainly by phosphatidylserine (PS) decarboxylase at the mitochondrial inner membrane. In Saccharomyces cerevisiae, PS is synthesized in the endoplasmic reticulum (ER), such that mitochondrial PE synthesis requires PS transport from the ER to the mitochondrial inner membrane. Here, we provide evidence that Ups2–Mdm35, a protein complex localized at the mitochondrial intermembrane space, mediates PS transport for PE synthesis in respiration-active mitochondria. UPS2- and MDM35-null mutations greatly attenuated conversion of PS to PE in yeast cells growing logarithmically under nonfermentable conditions, but not fermentable conditions. A recombinant Ups2–Mdm35 fusion protein exhibited phospholipid-transfer activity between liposomes in vitro. Furthermore, UPS2 expression was elevated under nonfermentable conditions and at the diauxic shift, the metabolic transition from glycolysis to oxidative phosphorylation. These results demonstrate that Ups2–Mdm35 functions as a PS transfer protein and enhances mitochondrial PE synthesis in response to the cellular metabolic state.