Mitochondrial dysfunction in ischaemia-reperfusion

Authors

  • N.-E. L. SARIS,

    Corresponding author
    1. The Helsinki Bioenergetics Group, Department of Medical Chemistry, Institute of Biomedicine, University of Helsinki, Helsinki, Finland
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  • K. O. ERIKSSON

    1. The Helsinki Bioenergetics Group, Department of Medical Chemistry, Institute of Biomedicine, University of Helsinki, Helsinki, Finland
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University of Helsinki Department of Medical Chemistry Institute of Biomedicine P. O. B. 8 FIN-00014 Helsinki, Finland

Abstract

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 M8 <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, prooxidants 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.

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