1. The GTPase RAB20 is a HIF target with mitochondrial localization mediating apoptosis in hypoxia.
- Author
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Hackenbeck T, Huber R, Schietke R, Knaup KX, Monti J, Wu X, Klanke B, Frey B, Gaipl U, Wullich B, Ferbus D, Goubin G, Warnecke C, Eckardt KU, and Wiesener MS
- Subjects
- Animals, Blotting, Western, Caspases metabolism, Cells, Cultured, Electrophoretic Mobility Shift Assay, Humans, Hypoxia metabolism, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Immunoenzyme Techniques, Luciferases metabolism, Mice, Mice, Inbred C57BL, Promoter Regions, Genetic, RNA, Messenger genetics, RNA, Small Interfering genetics, Reverse Transcriptase Polymerase Chain Reaction, rab GTP-Binding Proteins antagonists & inhibitors, rab GTP-Binding Proteins genetics, Apoptosis, Hypoxia pathology, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Mitochondria metabolism, rab GTP-Binding Proteins metabolism
- Abstract
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., (Copyright © 2010 Elsevier B.V. All rights reserved.)
- Published
- 2011
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