Mitochondrial dysfunction in ischaemia-reperfusion.
The mitochondrial dysfunction in ischaemia-reperfusion is shortly reviewed. During ischaemia the ATP level and pH drops, phospholipids are degraded, membrane permeabilities increased and the cytosolic levels of Na+ and Ca2+ raised. During the following reperfusion the Ca2+ levels may further increase while pH is raised. The oxidative phosphorylation is resumed and the ATP used for membrane repair and ion pumping. The mitochondrial Ca2+ handling is important in removing Ca2+ from the cytosol since the mitochondria are able to take up substantial amounts of Ca2+. However, if a certain threshold is exceeded, mitochondria undergo a so-called permeability transition (MPT), release their Ca2+, undergo swelling and become uncoupled. MPT has been shown to be due to the opening of large pore allowing passage of substances with a M(R) < 1500. Data are presented showing by electron microscopy swelling of mitochondria in cells in perfused liver before other gross morphological changes have taken place. There are a number of factors lowering the threshold for Ca2+ in inducing the MPT: inorganic phosphate, pro-oxidants that oxidize membrane SH-groups, oxidation of NAD(P)H and GSH, while a protective effect is exerted by Mg2+, ADP (and ATP), some antioxidants, carnitine, decrease in pH, and cyclosporin A that binds to cyclophilin. The potential benefit of these in minimizing reperfusion-induced tissue damage is discussed.
Saris
N E
NE
Department of Medical Chemistry, University of Helsinki, Finland.
Eriksson
K O
KO
D000255:Adenosine Triphosphate / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016623:Ion Pumps; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology*; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D008933:Mitochondrial Swelling; D010085:Oxidative Phosphorylation; D010539:Permeability; D010743:Phospholipids / Q000378:metabolism; D015424:Reperfusion; D012964:Sodium / Q000378:metabolism
D016623:Ion Pumps; D010743:Phospholipids; D000255:Adenosine Triphosphate; D012964:Sodium; D002118:Calcium