AIF deficiency compromises oxidative phosphorylation
AIF deficiency compromises oxidative phosphorylation
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DOI：
10.1038/sj.emboj.7600461
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发表时间：
2004-11-24
期刊：
影响因子：
11.4
通讯作者：
Kroemer, G
中科院分区：
文献类型：
--
作者：
Vahsen, N;Candé, C;Kroemer, G
凋亡诱导因子（Apoptosis-inducing factor，AIF）是一种线粒体黄素蛋白，在凋亡诱导后，其易位到细胞核，在那里其参与凋亡染色质溶解。在这里，我们表明，人类或小鼠细胞缺乏AIF作为同源重组或小干扰RNA的结果表现出高乳酸生产和糖酵解ATP生成的依赖性增强，由于呼吸链复合物I活性的严重降低。虽然AIF本身不是复合物I的一部分，但AIF缺陷细胞表现出复合物I及其组分的含量降低，这表明AIF在这种多蛋白复合物的生物发生和/或维持中的作用。由于逆转录病毒插入AIF基因而导致AIF表达降低的Harlequin小鼠也表现出视网膜和脑中氧化磷酸化（OXPHOS）降低，这与复合物I亚基的表达降低、视网膜变性和神经元缺陷相关。总之，这些数据表明AIF在OXPHOS中的作用，并强调AIF在生命和死亡中的双重作用。
Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein that, after apoptosis induction, translocates to the nucleus where it participates in apoptotic chromatinolysis. Here, we show that human or mouse cells lacking AIF as a result of homologous recombination or small interfering RNA exhibit high lactate production and enhanced dependency on glycolytic ATP generation, due to severe reduction of respiratory chain complex I activity. Although AIF itself is not a part of complex I, AIF-deficient cells exhibit a reduced content of complex I and of its components, pointing to a role of AIF in the biogenesis and/or maintenance of this polyprotein complex. Harlequin mice with reduced AIF expression due to a retroviral insertion into the AIF gene also manifest a reduced oxidative phosphorylation (OXPHOS) in the retina and in the brain, correlating with reduced expression of complex I subunits, retinal degeneration, and neuronal defects. Altogether, these data point to a role of AIF in OXPHOS and emphasize the dual role of AIF in life and death.