Home LiteratureArticle Details
PMID: 8117255 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

On the involvement of a mitochondrial pore in reperfusion injury.

Basic research in cardiology ·Vol. 88 ·No. 5 ·1993-00-00 ·Pages 513-23

Crompton M, Andreeva L

Abstract

We review evidence implicating mitochondrial dysfunction in the pathogenesis of ischaemia/reperfusion injury. The lesion has been identified as a non selective pore that is triggered by Ca2+ and particular metabolic derangements associated with this form of injury, namely falling ATP, raised Pi and oxidative stress. Once activated, the pore flickers between open and closed states and disrupts mitochondrial energy transduction, allowing ATP hydrolysis by the F1F0 ATPase. Pore activation is prevented by cyclosporin A, which also retards the onset of necrosis in heart cells subjected to substrate-free anoxia and allows partial regeneration of ATP on reoxygenation.

MeSH Terms
Animals Biological Transport Calcium/metabolism Cytosol/metabolism Mitochondria, Heart/metabolism,pathology Myocardial Ischemia/metabolism Myocardial Reperfusion Injury/etiology,pathology Myocardium/cytology,metabolism
Chemicals
Calcium
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Crompton M
Department of Biochemistry & Molecular Biology, University College London, United Kingdom.
Andreeva L
References (45)
45 references, click to expand
  1. Correlation between cytosolic free calcium, contracture, ATP, and irreversible ischemic injury in perfused rat heart.
    Circ Res. 1990 Jan;66(1):135-46 PMID: 2295135
  2. Modulation of the mitochondrial cyclosporin A-sensitive permeability transition pore by the proton electrochemical gradient. Evidence that the pore can be opened by membrane depolarization.
    J Biol Chem. 1992 May 5;267(13):8834-9 PMID: 1374381
  3. Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria.
    Biochem J. 1980 Nov 1;191(2):421-7 PMID: 6263247
  4. The presence of two classes of high-affinity cyclosporin A binding sites in mitochondria. Evidence that the minor component is involved in the opening of an inner-membrane Ca(2+)-dependent pore.
    Eur J Biochem. 1990 Dec 12;194(2):671-9 PMID: 2176603
  5. Studies on the electron transfer pathway, topography of iron-sulfur centers, and site of coupling in NADH-Q oxidoreductase.
    J Biol Chem. 1988 Nov 25;263(33):17566-75 PMID: 2846570
  6. Direct detection of free radicals in the reperfused rat heart using electron spin resonance spectroscopy.
    Circ Res. 1987 Nov;61(5):757-60 PMID: 2822281
  7. Improved procedure for determining glutathione in plasma as an index of myocardial oxidative stress.
    Clin Chem. 1987 Aug;33(8):1448-9 PMID: 3608163
  8. Modulation of inner mitochondrial membrane channel activity.
    J Bioenerg Biomembr. 1992 Feb;24(1):99-110 PMID: 1380510
  9. The nature of the calcium ion efflux induced in rat liver mitochondria by the oxidation of endogenous nicotinamide nucleotides.
    Biochem J. 1980 Apr 15;188(1):113-8 PMID: 7406874
  10. Action of cyclosporine on mitochondrial calcium fluxes.
    J Bioenerg Biomembr. 1987 Jun;19(3):297-303 PMID: 3114244
  11. Further characterization of contact sites from mitochondria of different tissues: topology of peripheral kinases.
    Biochim Biophys Acta. 1989 Jun 6;981(2):213-25 PMID: 2543459
  12. Cyclosporin A protects hepatocytes against prooxidant-induced cell killing. A study on the role of mitochondrial Ca2+ cycling in cytotoxicity.
    Biochem Pharmacol. 1992 Nov 17;44(10):1995-2003 PMID: 1449518
  13. Intracellular acidosis protects cultured hepatocytes from the toxic consequences of a loss of mitochondrial energization.
    Arch Biochem Biophys. 1989 Jul;272(1):152-61 PMID: 2735760
  14. The cationically selective state of the mitochondrial outer membrane pore: a study with intact mitochondria and reconstituted mitochondrial porin.
    Biochim Biophys Acta. 1990 Mar;1022(3):311-8 PMID: 1690571
  15. Quantitative microchemical imaging of calcium in Na-K pump inhibited heart cells.
    Cell Calcium. 1988 Dec;9(5-6):219-35 PMID: 2852062
  16. A heart mitochondrial Ca2(+)-dependent pore of possible relevance to re-perfusion-induced injury. Evidence that ADP facilitates pore interconversion between the closed and open states.
    Biochem J. 1990 Feb 15;266(1):33-9 PMID: 2106875
  17. Cyclosporin A protects hepatocytes subjected to high Ca2+ and oxidative stress.
    FEBS Lett. 1992 Jun 15;304(2-3):192-4 PMID: 1618322
  18. Measurement of mitochondrial free Ca2+ concentration in living single rat cardiac myocytes.
    Am J Physiol. 1991 Oct;261(4 Pt 2):H1123-34 PMID: 1928394
  19. Improvement of mitochondrial energy production in ischemic myocardium by in vivo infusion of ruthenium red.
    J Cardiovasc Pharmacol. 1980 Jan-Feb;2(1):45-54 PMID: 6154204
  20. Inhibition of Ca2(+)-induced large-amplitude swelling of liver and heart mitochondria by cyclosporin is probably caused by the inhibitor binding to mitochondrial-matrix peptidyl-prolyl cis-trans isomerase and preventing it interacting with the adenine nucleotide translocase.
    Biochem J. 1990 May 15;268(1):153-60 PMID: 2160810
  21. The effects of ruthenium red on mitochondrial function during post-ischaemic reperfusion.
    J Mol Cell Cardiol. 1982 Dec;14(12):737-40 PMID: 6187931
  22. Dehydrogenase activation by Ca2+ in cells and tissues.
    J Bioenerg Biomembr. 1991 Dec;23(6):823-54 PMID: 1778993
  23. Protection by cyclosporin A of cultured hepatocytes from the toxic consequences of the loss of mitochondrial energization produced by 1-methyl-4-phenylpyridinium.
    Biochem Pharmacol. 1992 Aug 18;44(4):833-5 PMID: 1510732
  24. Bioluminescent measurement in single cardiomyocytes of sudden cytosolic ATP depletion coincident with rigor.
    J Mol Cell Cardiol. 1992 Mar;24(3):213-8 PMID: 1625346
  25. Ca2+ transport by mammalian mitochondria and its role in hormone action.
    Am J Physiol. 1985 Dec;249(6 Pt 1):E543-54 PMID: 2417490
  26. The mitochondrial megachannel is the permeability transition pore.
    J Bioenerg Biomembr. 1992 Feb;24(1):111-7 PMID: 1380498
  27. cDNA sequence of a human skeletal muscle ADP/ATP translocator: lack of a leader peptide, divergence from a fibroblast translocator cDNA, and coevolution with mitochondrial DNA genes.
    Proc Natl Acad Sci U S A. 1987 Nov;84(21):7580-4 PMID: 2823266
  28. Calcium and magnesium transport by in situ mitochondria: electron probe analysis of vascular smooth muscle.
    Circ Res. 1987 Oct;61(4):523-30 PMID: 3652399
  29. Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl-pyridine, a metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine.
    Life Sci. 1985 Jul 1;36(26):2503-8 PMID: 2861548
  30. Mitochondrial benzodiazepine receptors and the regulation of steroid biosynthesis.
    Annu Rev Pharmacol Toxicol. 1992;32:211-37 PMID: 1318670
  31. Correlated effluxes of adenine nucleotides, Mg2+ and Ca2+ induced in rat-liver mitochondria by external Ca2+ and phosphate.
    Eur J Biochem. 1981 Feb;114(2):195-9 PMID: 7215353
  32. Involvement of the ADP/ATP carrier in calcium-induced perturbations of the mitochondrial inner membrane permeability: importance of the orientation of the nucleotide binding site.
    Arch Biochem Biophys. 1988 Sep;265(2):249-57 PMID: 2844116
  33. Allosteric inhibition of the Ca2+-activated hydrophilic channel of the mitochondrial inner membrane by nucleotides.
    J Membr Biol. 1980 Jun 15;54(3):231-6 PMID: 6248646
  34. Binding of [3H]Ro 5-4864 and [3H]PK 11195 to cerebral cortex and peripheral tissues of various species: species differences and heterogeneity in peripheral benzodiazepine binding sites.
    J Neurochem. 1987 Nov;49(5):1407-14 PMID: 2822854
  35. Nucleotide metabolism and cellular damage in myocardial ischemia.
    Annu Rev Physiol. 1985;47:727-49 PMID: 2581508
  36. The involvement of cyclosporin A binding proteins in regulating and uncoupling mitochondrial energy transduction.
    Biochim Biophys Acta. 1992 Jul 17;1101(2):214-7 PMID: 1633188
  37. Electrophysiological characterization of contact sites in brain mitochondria.
    J Biol Chem. 1990 Jan 15;265(2):908-13 PMID: 1688556
  38. Cytosolic free Ca2+ in single rat heart cells during anoxia and reoxygenation.
    Biochem J. 1987 Jun 1;244(2):381-5 PMID: 3663131
  39. Integration of porin synthesized in vitro into outer mitochondrial membranes.
    Eur J Biochem. 1987 Nov 2;168(3):509-14 PMID: 3665933
  40. Inhibition by cyclosporin A of a Ca2+-dependent pore in heart mitochondria activated by inorganic phosphate and oxidative stress.
    Biochem J. 1988 Oct 1;255(1):357-60 PMID: 3196322
  41. Isolation of the mitochondrial benzodiazepine receptor: association with the voltage-dependent anion channel and the adenine nucleotide carrier.
    Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3170-4 PMID: 1373486
  42. The entrapment of the Ca2+ indicator arsenazo III in the matrix space of rat liver mitochondria by permeabilization and resealing. Na+-dependent and -independent effluxes of Ca2+ in arsenazo III-loaded mitochondria.
    Biochem J. 1986 Oct 1;239(1):31-40 PMID: 3800984
  43. Inhibition of anoxia-induced injury in heart myocytes by cyclosporin A.
    J Mol Cell Cardiol. 1991 Dec;23(12):1351-4 PMID: 1811053
  44. Cytosolic free calcium in chick heart cells. Its role in cell injury.
    J Mol Cell Cardiol. 1985 Mar;17(3):221-31 PMID: 3837822
  45. Kinetic evidence for a heart mitochondrial pore activated by Ca2+, inorganic phosphate and oxidative stress. A potential mechanism for mitochondrial dysfunction during cellular Ca2+ overload.
    Eur J Biochem. 1988 Dec 15;178(2):489-501 PMID: 2850179
Article Info
Journal
Basic research in cardiology
Abbr.
Basic Res Cardiol
ISSN
0300-8428
DOI
10.1007/BF00795416
Published
1993-00-00
Pages
513-23
Language
English
Region
Germany
NLM ID
0360342
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00795416 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2