Oxygen sensors at the crossroad of metabolism.
Aerobic organisms developed mechanisms to protect themselves against a shortage of oxygen (O(2)). Recent studies reveal that O(2) sensors, belonging to the novel class of 2-oxoglutarate dependent iron(ii)-dioxygenases, have more important roles in metabolism than anticipated. Here, we provide a "metabolo-centric" overview of the role of the PHD/FIH members of this family in metabolism, in particular on how they regulate O(2) supply and consumption, energy compensation and conservation, O(2) conformance and hypoxia tolerance, redox and pH homeostasis, and other vital metabolic processes with implications in health and disease. These insights may offer novel opportunities for the treatment of ischemic diseases.
Aragonés
Julián
J
Vesalius Research Center, K.U. Leuven, Leuven, B-3000, Belgium.
Fraisl
Peter
P
Baes
Myriam
M
Carmeliet
Peter
P
D000818:Animals; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007511:Ischemia / Q000209:etiology; D051379:Mice; D010101:Oxygen Consumption; D010105:Oxygenases / Q000378:metabolism*; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism*; D015398:Signal Transduction
D005227:Fatty Acids; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010105:Oxygenases; C433124:iron(II) oxygenase; D011393:Procollagen-Proline Dioxygenase; D005947:Glucose