MICOS and phospholipid transfer by Ups2-Mdm35 organize membrane lipid synthesis in mitochondria.
MICOS and phospholipid transfer by Ups2-Mdm35 organize membrane lipid synthesis in mitochondria.
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MICOS和UPS2-MDM35在线粒体中组织膜脂质合成。
DOI：
10.1083/jcb.201602007
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发表时间：
2016-06-06
期刊：
影响因子：
--
通讯作者：
Tatsuta T
中科院分区：
文献类型：
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作者：
Aaltonen MJ;Friedman JR;Osman C;Salin B;di Rago JP;Nunnari J;Langer T;Tatsuta T
线粒体在脂质代谢中发挥重要作用，并促进细胞膜主要成分的合成，如磷脂酰乙醇胺(PE)。在这里，奥尔托宁等人。有两条途径参与了PE的合成：依赖于UPS2-MDM35的脂质转移和依赖于MICOS的膜结合。线粒体在细胞脂质代谢中发挥重要作用，促进细胞膜主要成分如磷脂酰乙醇胺(PE)和磷脂酰胆碱的合成。在这里，我们证明了位于线粒体膜内的磷脂酰丝氨酸脱羧酶Psd1通过两条途径促进线粒体PE的合成。首先，Ups2-Mdm35复合体(在人类中为SLMO2-TRIAP1)作为磷脂酰丝氨酸(PS)特异性脂转移蛋白在线粒体膜间间隙发挥作用，允许Psd1在内膜形成PE。第二，Psd1以反式方式使外膜中的PS脱羧基，而不依赖于Ups2-MDm35的PS转移。后一条途径需要线粒体膜与线粒体接触部位和线粒体脊组织系统(MICOS)紧密结合。在MICOS缺失的细胞中，限制Ups2-MDM35的PS转移和减少线粒体PE的积累可以保护线粒体的呼吸和脊的形成。这些结果将线粒体PE代谢与MICOS联系在一起，结合了蛋白质和脂肪稳态的功能，以保护线粒体的结构和功能。
Mitochondria exert critical functions in lipid metabolism and promote the synthesis of major constituents of cellular membranes, such as phosphatidylethanolamine (PE). Here, Aaltonen et al. demonstrate that two pathways mediate PE synthesis: Ups2–Mdm35–dependent lipid transfer and MICOS-dependent membrane apposition. Mitochondria exert critical functions in cellular lipid metabolism and promote the synthesis of major constituents of cellular membranes, such as phosphatidylethanolamine (PE) and phosphatidylcholine. Here, we demonstrate that the phosphatidylserine decarboxylase Psd1, located in the inner mitochondrial membrane, promotes mitochondrial PE synthesis via two pathways. First, Ups2–Mdm35 complexes (SLMO2–TRIAP1 in humans) serve as phosphatidylserine (PS)-specific lipid transfer proteins in the mitochondrial intermembrane space, allowing formation of PE by Psd1 in the inner membrane. Second, Psd1 decarboxylates PS in the outer membrane in trans, independently of PS transfer by Ups2–Mdm35. This latter pathway requires close apposition between both mitochondrial membranes and the mitochondrial contact site and cristae organizing system (MICOS). In MICOS-deficient cells, limiting PS transfer by Ups2–Mdm35 and reducing mitochondrial PE accumulation preserves mitochondrial respiration and cristae formation. These results link mitochondrial PE metabolism to MICOS, combining functions in protein and lipid homeostasis to preserve mitochondrial structure and function.