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Mitochondrial energy production and cation control in myocardial ischaemia and reperfusion
- Source :
- Basic research in cardiology. 88(5)
- Publication Year :
- 1993
-
Abstract
- In the heart mitochondria exert two roles essential for cell survival: ATP synthesis and maintainance of Ca2+ homeostasis. These two processes are driven by the same energy source: the H+ electrochemical gradient (delta microH) which is generated by electron transport along the inner mitochondrial membrane. Under aerobic physiological condition mitochondria do not contribute to the beat to beat regulation of cytosolic Ca2+, although Ca2+ transient in mitochondrial matrix has been described. Increases in mitochondrial Ca2+ of mumolars concentration stimulate the Krebs cycle and NADH redox potential and, therefore, ATP synthesis. Under pathological conditions, however, mitochondrial Ca2+ transport and overload might cause a series of vicious cycles leading to irreversible cell damage. Mitochondrial Ca2+ accumulation causes profound alterations in permeability of the inner membrane to solutes, leading to severe mitochondrial swelling. In addition Ca2+ transport takes precedence over ATP synthesis and inhibits utilization of delta microH for energy production. These processes are important to understand the sequence of the molecular events occurring during myocardial reperfusion after prolonged ischaemia which lead to irreversible cell damage. During ischaemia an alteration of intracellular Ca2+ homeostasis occurs and mitochondria are able to buffer cytosolic Ca2+, suggesting that they retain the Ca2+ transporting capacity. Accordingly, once isolated, even after prolonged ischaemia, the majority of the mitochondria is able to use oxygen for ATP phosphorylation. When isolated after reperfusion, mitochondria are structurally altered, contain large quantities of Ca2+, produce excess of oxygen free radicals, their membrane pores are stimulated and the oxidative phosphorylation capacity is irreversibly disrupted. Most likely, reperfusion provides oxygen to reactivate mitochondrial respiration but also causes large influx of Ca2+ in the cytosol as result of sarcolemmal damage. Mitochondrial Ca2+ transport is therefore stimulated at maximal rates and, as consequence, the equilibrium between ATP synthesis and Ca2+ influx is shifted towards Ca2+ influx with loss of the ability of ATP synthesis.
- Subjects :
- medicine.medical_specialty
Physiology
Myocardial Ischemia
Myocardial Reperfusion
Oxidative phosphorylation
Mitochondrion
Mitochondria, Heart
Adenosine Triphosphate
Physiology (medical)
Internal medicine
Cations
medicine
Animals
Homeostasis
Electrochemical gradient
Inner mitochondrial membrane
Ion transporter
ATP synthase
biology
Chemistry
Biological Transport
Electron transport chain
Endocrinology
Mitochondrial matrix
Biophysics
biology.protein
Calcium
Protons
Cardiology and Cardiovascular Medicine
Energy Metabolism
Subjects
Details
- ISSN :
- 03008428
- Volume :
- 88
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Basic research in cardiology
- Accession number :
- edsair.doi.dedup.....a8987a73581a2fddf5f6bfcbf6fca013