The GTPase RAB20 is a HIF target with mitochondrial localization mediating apoptosis in hypoxia.
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.
University of Erlangen-Nuremberg, Erlangen, Germany.
Thomas
T
Hackenbeck
Regina
R
Huber
Ruth
R
Schietke
Karl X
KX
Knaup
Juliana
J
Monti
Xiaoqing
X
Wu
Bernd
B
Klanke
Benjamin
B
Frey
Udo
U
Gaipl
Bernd
B
Wullich
Didier
D
Ferbus
Gérard
G
Goubin
Christina
C
Warnecke
Kai-Uwe
KU
Eckardt
Michael S
MS
Wiesener
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020691:rab GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D008156:Luciferases; D020169:Caspases; C509832:Rab20 protein, human; C092933:Rab20 protein, mouse; D020691:rab GTP-Binding Proteins