Mitochondrial CDP-diacylglycerol synthase activity is due to the peripheral protein, TAMM41 and not due to the integral membrane protein, CDP-diacylglycerol synthase 1.
Mitochondrial CDP-diacylglycerol synthase activity is due to the peripheral protein, TAMM41 and not due to the integral membrane protein, CDP-diacylglycerol synthase 1.
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DOI：
10.1016/j.bbalip.2017.12.005
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Cockcroft S
中科院分区：
文献类型：
--
作者：
Blunsom NJ;Gomez-Espinosa E;Ashlin TG;Cockcroft S
CDP二酰甘油合成酶(CDS)催化磷脂酸(PA)转化为CDP二酰甘油，CDP二甘油是合成磷脂酰甘油、心磷脂和磷脂酰肌醇(PI)的重要中间体。在哺乳动物细胞的线粒体和内质网中已经发现了CDS的活性，显然是由两个高度相关的基因CDS1和CDS2编码的。心磷脂仅在线粒体中合成，最近在心肌细胞中的研究表明，过氧化物酶体增殖物激活受体γ辅活化子1(PGC-1α和β)是线粒体生物发生的转录调节因子，上调CDS1基因的转录。在这里，我们研究了CDS1是否与线粒体CDS活性有关。我们报道了维甲酸诱导H9c2细胞向心肌细胞分化的过程中，伴随着线粒体蛋白表达增加、氧耗量增加以及PA/PI结合蛋白PITPNC1和CDS1免疫反应性的增加。H9c2细胞线粒体及大鼠心、肝、脑线粒体均有CDS1免疫反应和CDS活性。然而，CDS1的免疫反应被追溯到外周P55交叉反应的线粒体蛋白，而线粒体CDS的活性是由于外周线粒体蛋白TAMM41，而不是CDS1预期的完整的膜蛋白。TAMM41是最近发现的酵母蛋白Tam41在哺乳动物中的等价物。TAMM41基因敲除后线粒体CDS活性降低，心磷脂水平降低，氧耗量减少。我们得出结论，线粒体中CDS活性的存在主要是由于TAMM41，它是正常线粒体功能所必需的。
CDP diacylglycerol synthase (CDS) catalyses the conversion of phosphatidic acid (PA) to CDP-diacylglycerol, an essential intermediate in the synthesis of phosphatidylglycerol, cardiolipin and phosphatidylinositol (PI). CDS activity has been identified in mitochondria and endoplasmic reticulum of mammalian cells apparently encoded by two highly-related genes, CDS1 and CDS2. Cardiolipin is exclusively synthesised in mitochondria and recent studies in cardiomyocytes suggest that the peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1α and β) serve as transcriptional regulators of mitochondrial biogenesis and up-regulate the transcription of the CDS1 gene. Here we have examined whether CDS1 is responsible for the mitochondrial CDS activity. We report that differentiation of H9c2 cells with retinoic acid towards cardiomyocytes is accompanied by increased expression of mitochondrial proteins, oxygen consumption, and expression of the PA/PI binding protein, PITPNC1, and CDS1 immunoreactivity. Both CDS1 immunoreactivity and CDS activity were found in mitochondria of H9c2 cells as well as in rat heart, liver and brain mitochondria. However, the CDS1 immunoreactivity was traced to a peripheral p55 cross-reactive mitochondrial protein and the mitochondrial CDS activity was due to a peripheral mitochondrial protein, TAMM41, not an integral membrane protein as expected for CDS1. TAMM41 is the mammalian equivalent of the recently identified yeast protein, Tam41. Knockdown of TAMM41 resulted in decreased mitochondrial CDS activity, decreased cardiolipin levels and a decrease in oxygen consumption. We conclude that the CDS activity present in mitochondria is mainly due to TAMM41, which is required for normal mitochondrial function.
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影响因子：
3.3
作者：
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