The GTPase RAB20 is a HIF target with mitochondrial localization mediating apoptosis in hypoxia
The GTPase RAB20 is a HIF target with mitochondrial localization mediating apoptosis in hypoxia
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DOI：
10.1016/j.bbamcr.2010.10.019
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发表时间：
2011-01-01
影响因子：
5.1
通讯作者：
Wiesener, Michael S.
中科院分区：
文献类型：
--
作者：
Hackenbeck, Thomas;Huber, Regina;Wiesener, Michael S.
低氧是一种常见的致病应激，需要低氧诱导转录因子(HIF)的适应性激活。同时，转录的HIF靶标提高了氧气的可获得性，同时减少了氧气需求，使其能够在低氧微环境中存活。在这里，我们描述了一个新的HIF-1靶基因Rab20的特征，它是小GTP结合蛋白Rab家族的成员，调节细胞内运输和囊泡形成。Rab20受HIF-1的直接调控，在低氧条件下可迅速上调Rab20mRNA和蛋白的表达。此外，外源和内源Rab20蛋白都与线粒体共存。基因敲除研究表明，Rab20参与了低氧诱导的细胞凋亡。由于线粒体在细胞死亡的控制中起着关键作用，我们认为在低氧条件下调节线粒体的动态平衡是Rab20的关键功能。此外，我们的研究表明，细胞运输途径在氧稳态中发挥着作用。低氧诱导的Rab20在低氧应激过程中和低氧应激后可能会影响组织的稳态和修复。(C)2010爱思唯尔B.V.保留所有权利。
Hypoxia is a common pathogenic stress, which requires adaptive activation of the Hypoxia-inducible transcription factor (HIF). In concert transcriptional HIF targets enhance oxygen availability and simultaneously reduce oxygen demand, enabling survival in a hypoxic microenvironment. Here, we describe the characterization of a new HIF-1 target gene, Rab20, which is a member of the Rab family of small GTP-binding proteins, regulating intracellular trafficking and vesicle formation. Rab20 is directly regulated by HIF-1, resulting in rapid upregulation of Rab20 mRNA as well as protein under hypoxia. Furthermore, exogenous as well as endogenous Rab20 protein colocalizes with mitochondria. Knockdown studies reveal that Rab20 is involved in hypoxia induced apoptosis. Since mitochondria play a key role in the control of cell death, we suggest that regulating mitochondrial homeostasis in hypoxia is a key function of Rab20. Furthermore, our study implicates that cellular transport pathways play a role in oxygen homeostasis. Hypoxia-induced Rab20 may influence tissue homeostasis and repair during and after hypoxic stress. (C) 2010 Elsevier B.V. All rights reserved.