An essential bacterial-type cardiolipin synthase mediates cardiolipin formation in a eukaryote

An essential bacterial-type cardiolipin synthase mediates cardiolipin formation in a eukaryote
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一种必需的细菌型心磷脂合酶介导真核生物中的心磷脂形成

DOI:
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发表时间:
2012
影响因子:
11.1
通讯作者:
P. Bütikofer
P. Bütikofer
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Mauro Serricchio;P. Bütikofer

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心磷脂对于细菌和线粒体的稳定性和功能是重要的。心磷脂生物合成的最后一步是由心磷脂合酶催化的,原核生物和真核生物之间的机制不同。为了研究心磷脂合成对人类和动物病原性原生动物寄生虫布氏锥虫线粒体完整性、膜蛋白复合物形成和细胞增殖的重要性,我们产生了条件性心磷脂酶敲除寄生虫。我们发现T.布鲁氏菌前环形式由细菌型心磷脂合酶催化,为真核生物中的原核型心磷脂合酶提供了实验证据。酶表达的消融导致从头心磷脂合成的抑制,细胞心磷脂水平的降低,线粒体形态和功能的改变,以及培养中的寄生虫死亡。通过使用免疫荧光显微镜和蓝色天然凝胶电泳,心磷脂合酶被证明与线粒体内膜蛋白共定位,并成为一个大的蛋白质复合物的一部分。在耗尽的心磷脂合酶,细胞色素氧化酶亚基IV和细胞色素C1的水平,反映线粒体呼吸复合物IV和III,分别逐步下降。
Cardiolipin is important for bacterial and mitochondrial stability and function. The final step in cardiolipin biosynthesis is catalyzed by cardiolipin synthase and differs mechanistically between prokaryotes and eukaryotes. To study the importance of cardiolipin synthesis for mitochondrial integrity, membrane protein complex formation, and cell proliferation in the human and animal pathogenic protozoan parasite, Trypanosoma brucei, we generated conditional cardiolipin synthase-knockout parasites. We found that cardiolipin formation in T. brucei procyclic forms is catalyzed by a bacterial-type cardiolipin synthase, providing experimental evidence for a prokaryotic-type cardiolipin synthase in a eukaryotic organism. Ablation of enzyme expression resulted in inhibition of de novo cardiolipin synthesis, reduction in cellular cardiolipin levels, alterations in mitochondrial morphology and function, and parasite death in culture. By using immunofluorescence microscopy and blue-native gel electrophoresis, cardiolipin synthase was shown to colocalize with inner mitochondrial membrane proteins and to be part of a large protein complex. During depletion of cardiolipin synthase, the levels of cytochrome oxidase subunit IV and cytochrome c1, reflecting mitochondrial respiratory complexes IV and III, respectively, decreased progressively.
来自大肠杆菌的心磷脂合酶。
DOI: 10.1016/s0005-2760(97)00100-8
发表时间: 1997
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影响因子: --
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影响因子: 3.4
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发表时间: 1990
期刊: Biochemistry
影响因子: 2.9
作者:
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通讯作者: Talbert,LH