The genetic interactome of prohibitins: coordinated control of cardiolipin and phosphatidylethanolamine by conserved regulators in mitochondria.
The genetic interactome of prohibitins: coordinated control of cardiolipin and phosphatidylethanolamine by conserved regulators in mitochondria.
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DOI：
10.1083/jcb.200810189
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发表时间：
2009-02-23
期刊：
影响因子：
--
通讯作者：
Langer T
中科院分区：
文献类型：
--
作者：
Osman C;Haag M;Potting C;Rodenfels J;Dip PV;Wieland FT;Brügger B;Westermann B;Langer T
线粒体内膜中的抑制素环复合物调节细胞增殖以及线粒体的动力学和功能。虽然阿糖胞苷在高等真核生物中是必需的，但阿糖胞苷缺陷的酵母细胞是可行的，并且表现出减少的复制寿命。在这里，我们定义的遗传相互作用的酵母中使用合成的遗传阵列，并确定35个遗传相互作用的酵母（GEP基因）所需的细胞生存在没有酵母的酵母。这些基因编码的蛋白质包括一个保守的蛋白质家族成员，Ups1和Gep1，其影响动力蛋白样GT3 Mgm1的加工，从而调节嵴形态发生。我们发现，Ups1和Gep1调节心磷脂和磷脂酰乙醇胺在线粒体中的脂质特异性，但协调的方式。通过质谱分析GEP缺陷型线粒体的脂质分布揭示了心磷脂和磷脂酰乙醇胺对胆固醇缺乏型细胞存活的关键作用。我们认为，白藜芦醇通过充当蛋白质和脂质支架来控制内膜组织和完整性。
Prohibitin ring complexes in the mitochondrial inner membrane regulate cell proliferation as well as the dynamics and function of mitochondria. Although prohibitins are essential in higher eukaryotes, prohibitin-deficient yeast cells are viable and exhibit a reduced replicative life span. Here, we define the genetic interactome of prohibitins in yeast using synthetic genetic arrays, and identify 35 genetic interactors of prohibitins (GEP genes) required for cell survival in the absence of prohibitins. Proteins encoded by these genes include members of a conserved protein family, Ups1 and Gep1, which affect the processing of the dynamin-like GTPase Mgm1 and thereby modulate cristae morphogenesis. We show that Ups1 and Gep1 regulate the levels of cardiolipin and phosphatidylethanolamine in mitochondria in a lipid-specific but coordinated manner. Lipid profiling by mass spectrometry of GEP-deficient mitochondria reveals a critical role of cardiolipin and phosphatidylethanolamine for survival of prohibitin-deficient cells. We propose that prohibitins control inner membrane organization and integrity by acting as protein and lipid scaffolds.
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影响因子：
5.3
作者：
Gulshan, Kailash;Schmidt, Jennifer A.;Moye-Rowley, W. Scott
通讯作者：
Moye-Rowley, W. Scott
影响因子：
12.4
作者：
Choi, S-Y;Gonzalvez, F.;Frohman, M. A.
通讯作者：
Frohman, M. A.
影响因子：
3.7
作者：
Kasashima, Katsumi;Sumitani, Megumi;Endo, Hitoshi
通讯作者：
Endo, Hitoshi
影响因子：
4.8
作者：
Kasashima, Katsumi;Ohta, Eriko;Endo, Hitoshi
通讯作者：
Endo, Hitoshi
影响因子：
9.2
作者：
Coates, PJ;Jamieson, DJ;Hall, PA
通讯作者：
Hall, PA