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Mitochondrial dysfunction in ischaemia‐reperfusion
Author(s) -
SARIS N.E. L.,
ERIKSSON K. O.
Publication year - 1995
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/j.1399-6576.1995.tb04353.x
Subject(s) - mitochondrion , cytosol , oxidative phosphorylation , mitochondrial permeability transition pore , nad+ kinase , ischemia , biophysics , biochemistry , membrane potential , medicine , chemistry , biology , enzyme , apoptosis , programmed cell death
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 Ca 2+ raised. During the following reperfusion the Ca 2+ 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 Ca 2+ handling is important in removing Ca 2+ from the cytosol since the mitochondria are able to take up substantial amounts of Ca 2 *. However, if a certain threshold is exceeded, mitochondria undergo a so‐called permeability transition (MPT), release their Ca 2+ , 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 8 <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 Ca 2+ in inducing the MPT: inorganic phosphate, prooxidants that oxidize membrane SH‐groups, oxidation of NAD(P)H and GSH, while a protective effect is exerted by Mg 2+ , 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.