Apoptosis-inducing factor (AIF):: a novel caspase-independent death effector released from mitochondria
Apoptosis-inducing factor (AIF):: a novel caspase-independent death effector released from mitochondria
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DOI：
10.1016/s0300-9084(02)01374-3
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发表时间：
2002-02-01
期刊：
影响因子：
3.9
通讯作者：
Kroemer, G
中科院分区：
文献类型：
--
作者：
Candé, C;Cohen, I;Kroemer, G
凋亡诱导因子（AIF）是一种在进化上古老的线粒体膜间黄素蛋白，当加入到纯化的细胞核中时，具有独特的能力诱导不依赖半胱天冬酶的外周染色质凝聚和大规模DNA断裂。除了对细胞核的促凋亡活性外，AIF还可参与对凋亡性线粒体膜通透性的调节，并表现出NADH氧化酶活性。在正常情况下，AIF位于线粒体外膜之后。然而，在诱导凋亡时，AIF转位到细胞质和细胞核。注射抗AIF抗体或敲除AIF基因已表明，AIF可能是某些刺激下细胞死亡所必需的。特别是，AIF失活使胚胎干细胞在生长因子撤除后对细胞死亡具有抗性。此外，AIF对于拟胚体空化过程中的程序性细胞死亡是必不可少的，这是小鼠形态发生所必需的（不依赖半胱天冬酶的）第一波细胞死亡。我们最近发现，AIF被热休克蛋白（HSP）70中和，这一反应似乎不依赖于ATP或HSP70的ATP结合结构域（ABD），因此不同于先前描述的Apaf - 1/HSP70相互作用（后者需要ATP和HSP70的ABD）。有趣的是，缺乏ABD的HSP70（HSP70ΔABD）抑制由血清撤除、星形孢菌素和甲萘醌诱导的凋亡，这三种凋亡模型也受抗AIF抗体微量注射或AIF基因敲除的影响。总之，这些数据表明AIF在不依赖半胱天冬酶的细胞死亡调节中起作用。（C）2002法国生物化学与分子生物学学会/科学与医学出版社爱思唯尔SAS。保留所有权利。
Apoptosis-inducing factor (AIF) is a phylogenetically ancient mitochondrial intermembrane flavoprotein endowed with the unique capacity to induce caspase-independent peripheral chromatin condensation and large-scale DNA fragmentation when added to purified nuclei. In addition to its apoptogenic activity on nuclei, AIF can also participate in the regulation of apoptotic mitochondrial membrane permeabilization and exhibits an NADH oxidase activity. Under normal circumstances, AIF is secluded behind the outer mitochondrial membrane. However, upon apoptosis induction AIF translocates to the cytosol and the nucleus. Injection of anti-AIF antibodies or knockout of the AIF gene have demonstrated that AIF may be required for cell death occurring in response to some stimuli. In particular, inactivation of AIF renders embryonic stern cells resistant to cell death following growth factor withdrawal. Moreover, AIF is essential for programmed cell death during cavitation of embryoid bodies, the very first wave of (caspase-independent) cell death indispensable for Mouse morphogenesis. We have recently found that AIF is neutralized by heat-shock protein (HSP) 70, in a reaction that appears to be independent of ATP or the ATP-binding domain (ABD) of HSP70 and thus differs from the previously described Apaf-1/HSP70 interaction (which requires ATP and the HSP70 ABD). Intriguingly, HSP70 lacking ABD (HSP70DeltaABD) inhibits apoptosis induced by serum withdrawal, staurosporin, and menadione. three models of apoptosis which are also affected by micro-injection of anti-AIF antibody or genetic ablation of AIF. Altogether, these data suggest that AIF plays a role in the regulation of caspase-independent cell death. (C) 2002 Societe francaise de biochimie et biologie moleculaire / Editions scientifiques et medicales Elsevier SAS. All rights reserved.