Hackenbeck Thomas, Huber Regina, Schietke Ruth, Knaup Karl X, Monti Juliana, Wu Xiaoqing, Klanke Bernd, Frey Benjamin, Gaipl Udo, Wullich Bernd, Ferbus Didier, Goubin Gérard, Warnecke Christina, Eckardt Kai-Uwe, Wiesener Michael S
University of Erlangen-Nuremberg, Erlangen, Germany.
Biochim Biophys Acta. 2011 Jan;1813(1):1-13. doi: 10.1016/j.bbamcr.2010.10.019. Epub 2010 Nov 5.
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.
缺氧是一种常见的致病应激，需要缺氧诱导转录因子（HIF）进行适应性激活。转录协同作用时，HIF靶标可提高氧利用率并同时降低氧需求，从而使人在缺氧微环境中存活。在此，我们描述了一种新的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直接调控，导致缺氧条件下Rab20 mRNA以及蛋白质迅速上调。此外，外源性和内源性Rab20蛋白均与线粒体共定位。敲低研究表明，Rab20参与缺氧诱导的细胞凋亡。由于线粒体在细胞死亡控制中起关键作用，我们认为在缺氧状态下调节线粒体稳态是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起作用。缺氧诱导的Rab20可能会影响缺氧应激期间及之后的组织稳态和修复。
