Porin proteins have critical functions in mitochondrial phospholipid metabolism in yeast
Porin proteins have critical functions in mitochondrial phospholipid metabolism in yeast
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DOI：
10.1074/jbc.ra118.005410
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发表时间：
2018-11-09
影响因子：
4.8
通讯作者：
Kuge, Osamu
中科院分区：
文献类型：
--
作者：
Miyata, Non;Fujii, Satoru;Kuge, Osamu
心磷脂（CL）和磷脂酰乙醇胺的线粒体合成需要将其前体磷脂酸和磷脂酰丝氨酸分别转运到线粒体内膜。在酵母中，Ups 1-Mdm 35和Ups 2-Mdm 35复合物分别在线粒体外膜和内膜之间转移磷脂酸和磷脂酰丝氨酸。此外，一个Ups 1独立的CL积累途径需要几个功能未知的线粒体蛋白，包括Mdm 31。在这里，我们确定了一个线粒体孔蛋白，Por 1，作为一种蛋白质，与Mdm 31和Mdm 35在芽殖酵母（酿酒酵母）相互作用。孔蛋白Por 1和Por 2的耗尽使Ups 1和Ups 2不稳定，使CL水平降低约90%，并导致Ups 2依赖性磷脂酰乙醇胺合成的损失，但不影响线粒体中Ups 2独立性磷脂酰乙醇胺合成。Por 1突变影响其与Mdm 31和Mdm 35的相互作用，但不影响呼吸生长，也降低了CL水平。使用HeLa细胞，我们表明，哺乳动物孔蛋白也在线粒体CL代谢的功能。我们的结论是酵母孔蛋白在线粒体磷脂代谢中具有特定且关键的功能，并且孔蛋白介导的CL代谢调节似乎在进化上是保守的。
Mitochondrial synthesis of cardiolipin (CL) and phosphatidylethanolamine requires the transport of their precursors, phosphatidic acid and phosphatidylserine, respectively, to the mitochondrial inner membrane. In yeast, the Ups1-Mdm35 and Ups2-Mdm35 complexes transfer phosphatidic acid and phosphatidylserine, respectively, between the mitochondrial outer and inner membranes. Moreover, a Ups1-independent CL accumulation pathway requires several mitochondrial proteins with unknown functions including Mdm31. Here, we identified a mitochondrial porin, Por1, as a protein that interacts with both Mdm31 and Mdm35 in budding yeast (Saccharomyces cerevisiae). Depletion of the porins Por1 and Por2 destabilized Ups1 and Ups2, decreased CL levels by approximate to 90%, and caused loss of Ups2-dependent phosphatidylethanolamine synthesis, but did not affect Ups2-independent phosphatidylethanolamine synthesis in mitochondria. Por1 mutations that affected its interactions with Mdm31 and Mdm35, but not respiratory growth, also decreased CL levels. Using HeLa cells, we show that mammalian porins also function in mitochondrial CL metabolism. We conclude that yeast porins have specific and critical functions in mitochondrial phospholipid metabolism and that porin-mediated regulation of CL metabolism appears to be evolutionarily conserved.