Surviving hypoxia without really dying.
In cases of severe O(2) limitation, most excitable cells of mammals cannot continue to meet the energy demands of active ion transporting systems, leading to catastrophic membrane failure and cell death. However, in certain lower vertebrates, hypoxia-induced membrane destabilisation of the kind seen in mammals is either slow to develop or does not occur at all owing to adaptive decreases in membrane permeability (i.e. ion 'channel arrest'), that dramatically reduce the energetic costs of ion-balancing ATPases. Mammalian cells do, however, exhibit a whole host of adaptive responses to less severe shortages of oxygen, which include energy-balanced metabolic suppression, ionic-induced activation of O(2) receptors and the upregulation of certain genes, all of which enhance the systemic delivery of oxygen and promote energy conservation. Accumulating evidence suggests that the mechanisms underlying these protective effects are orchestrated into action by putative members of an O(2)-sensing pathway that most if not all cells share in common. In this review we address three major questions: (i) how do cells detect shortages of oxygen and subsequently set in motion adaptive mechanisms of either energy production or energy conservation; (ii) how do these mechanisms restructure cellular pathways of ATP supply and demand to ensure that ion-motive ATPases are given priority over other cell functions to preserve membrane integrity in energy-limited states; and (iii) what mechanisms of molecular and metabolic defence against acute and long-term shortages of oxygen set hypoxia-tolerant systems apart from their hypoxia-sensitive counterparts?
Boutilier
R G
RG
Department of Zoology, University of Cambridge, Downing Street, CB2 3EJ, Cambridge, UK. rgb11@hermes.cam.ac.uk
St-Pierre
J
J
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D006180:Proton-Translocating ATPases / Q000378:metabolism
D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases