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Mitochondrial dysfunction in ischaemia-reperfusion.

N E Saris·K O Eriksson
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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 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.

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Adenosine TriphosphateCalciumCytosolHumansHydrogen-Ion ConcentrationIon PumpsIschemiaMitochondriaMitochondrial SwellingOxidative PhosphorylationPermeabilityPhospholipidsReperfusionSodiumJournal ArticleReview

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BibTeXRIS

N E Saris, K O Eriksson. 1995. Mitochondrial dysfunction in ischaemia-reperfusion.. https://doi.org/10.1111/j.1399-6576.1995.tb04353.x

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