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Aragones 2008 Nat Genet
Coupling states LEAK  + , OXPHOS  + , ET  +
Enzyme Complex I  +
Has abstract HIF prolyl hydroxylases (PHD1-3) are oxyge
HIF prolyl hydroxylases (PHD1-3) are oxygen sensors that regulate the stability of the hypoxia-inducible factors (HIFs) in an oxygen-dependent manner. Here, we show that loss of Phd1 lowers oxygen consumption in skeletal muscle by reprogramming glucose metabolism from oxidative to more anaerobic ATP production through activation of a Pparα pathway. This metabolic adaptation to oxygen conservation impairs oxidative muscle performance in healthy conditions, but it provides acute protection of myofibers against lethal ischemia. Hypoxia tolerance is not due to HIF-dependent angiogenesis, erythropoiesis or vasodilation, but rather to reduced generation of oxidative stress, which allows Phd1-deficient myofibers to preserve mitochondrial respiration. Hypoxia tolerance relies primarily on Hif-2α and was not observed in heterozygous Phd2-deficient or homozygous Phd3-deficient mice. Of medical importance, conditional knockdown of Phd1 also rapidly induces hypoxia tolerance. These findings delineate a new role of Phd1 in hypoxia tolerance and offer new treatment perspectives for disorders characterized by oxidative stress.
sorders characterized by oxidative stress.  +
Has info [http://www.ncbi.nlm.nih.gov/pubmed/181765
[http://www.ncbi.nlm.nih.gov/pubmed/18176562 PMID: 18176562]; [https://lirias.kuleuven.be/bitstream/123456789/145976/2/ng.2007.62.pdf PMID: 18176562 Open Access]; »[[File:O2k-brief.png|36px|link=http://www.bioblast.at/images/9/96/Aragones_2008-Nat_Genet_O2k-brief.pdf |O2k-brief]]
_2008-Nat_Genet_O2k-brief.pdf |O2k-brief]]  +
Has publicationkeywords Oxygen stress  + , Hypoxia tolerance  +
Has title Aragonés J, Schneider M, Van Geyte K, Frai
Aragonés J, Schneider M, Van Geyte K, Fraisl P, Dresselaers T, Mazzone M, Dirkx R, Zacchigna S, Lemieux H, Jeoung NH, Lambrechts D, Bishop T, Lafuste P, Diez-Juan A, K Harten S, Van Noten P, De Bock K, Willam C, Tjwa M, Grosfeld A, Navet R, Moons L, Vandendriessche T, Deroose C, Wijeyekoon B, Nuyts J, Jordan B, Silasi-Mansat R, Lupu F, Dewerchin M, Pugh C, Salmon P, Mortelmans L, Gallez B, Gorus F, Buyse J, Sluse F, Harris RA, Gnaiger E, Hespel P, Van Hecke P, Schuit F, Van Veldhoven P, Ratcliffe P, Baes M, Maxwell P, Carmeliet P (2008) Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism. Nat Genet 40:170-80.
ing basal metabolism. Nat Genet 40:170-80.  +
Instrument and method Oxygraph-2k  +
Mammal and model Mouse  +
MiP area Respiration  + , mt-Biogenesis;mt-density  + , Genetic knockout;overexpression  +
Pathways N  + , S  + , NS  +
Preparation Permeabilized tissue  +
Respiration and regulation Aerobic glycolysis  +
Stress Ischemia-reperfusion  + , Oxidative stress;RONS  +
Tissue and cell Skeletal muscle  +
Was published by MiPNetLab AT Innsbruck Gnaiger E + , CA Edmonton Lemieux H +
Was published in journal Nat Genet +
Was published in year 2008  +
Was written by Aragones Lopez J + , Schneider M + , Van Geyte K + , Fraisl P + , Dresselaers T + , Mazzone M + , Dirkx R + , Zacchigna S + , Lemieux H + , Jeoung NH + , Lambrechts D + , Bishop T + , Lafuste P + , Diez-Juan A + , K Harten S + , Van Noten P + , De Bock K + , Willam C + , Tjwa M + , Grosfeld A + , Navet R + , Moons L + , Vandendriessche T + , Deroose C + , Wijeyekoon B + , Nuyts J + , Jordan B + , Silasi-Mansat R + , Lupu F + , Dewerchin M + , Pugh C + , Salmon P + , Mortelmans L + , Gallez B + , Gorus F + , Buyse J + , Sluse F + , Harris RA + , Gnaiger E + , Hespel P + , Van Hecke P + , Schuit F + , Van Veldhoven P + , Ratcliffe P + , Baes M + , Maxwell P + , Carmeliet P +
Categories Publications
Modification date
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09:54:20, 10 April 2019  +
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