The good, the bad and the ugly in oxygen-sensing: ROS, cytochromes and prolyl-hydroxylases.
Current concepts of cellular oxygen-sensing include an isoform of the neutrophil NADPH oxidase, different electron carrier units of the mitochondrial electron transport chain (ETC), heme oxygenase-2 (HO-2), and a subfamily of 2-oxoglutarate dependent dioxygenases termed HIF (hypoxia inducible factor) prolyl hydroxylases (PHDs) and HIF asparagyl hydroxylase FIH-1 (factor-inhibiting HIF). Different oxygen sensitivities, cell-specific distribution and subcellular localization of specific oxygen-sensing cascades involving reactive oxygen species (ROS) as second messengers may help to tailor various adaptive responses according to differences in tissue oxygen availability. Herein, we propose an integrated model for these various oxygen-sensing mechanisms that very efficiently regulate HIF-alpha activity and plasma membrane potassium-channel (PMPC) conductivity.
Acker
Till
T
Neurologisches Institut, Edinger Institut, Klinikum der J.W. Goethe Universität Frankfurt am Main, Deutschordenstr. 46, D-60528 Frankfurt, Germany.
Fandrey
Joachim
J
Acker
Helmut
H
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D003580:Cytochromes / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D003580:Cytochromes; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015221:Potassium Channels; D017382:Reactive Oxygen Species; D011393:Procollagen-Proline Dioxygenase; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2; D010100:Oxygen