Mitochondrial energy production and cation control in myocardial ischaemia and reperfusion

R. Ferrari, P. Pedersini, M. Bongrazio, G. Gaia, P. Bernocchi, F. Di Lisa, O. Visioli

Research output: Contribution to journalArticle

56 Citations (Scopus)

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 (ΔμH) 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 μmolars 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 ΔμH 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.

Original languageEnglish
Pages (from-to)495-512
Number of pages18
JournalBasic Research in Cardiology
Volume88
Issue number5
DOIs
Publication statusPublished - Sep 1993

Fingerprint

Myocardial Reperfusion
Myocardial Ischemia
Cations
Adenosine Triphosphate
Mitochondria
Ischemia
Reperfusion
Homeostasis
Mitochondrial Swelling
Oxygen
Heart Mitochondria
Citric Acid Cycle
Membranes
Oxidative Phosphorylation
Mitochondrial Membranes
Electron Transport
NAD
Cytosol
Oxidation-Reduction
Free Radicals

Keywords

  • Ca metabolism
  • energy production
  • Heart mitochondria
  • myocardial ischaemia
  • myocardial reperfusion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Mitochondrial energy production and cation control in myocardial ischaemia and reperfusion. / Ferrari, R.; Pedersini, P.; Bongrazio, M.; Gaia, G.; Bernocchi, P.; Di Lisa, F.; Visioli, O.

In: Basic Research in Cardiology, Vol. 88, No. 5, 09.1993, p. 495-512.

Research output: Contribution to journalArticle

Ferrari, R, Pedersini, P, Bongrazio, M, Gaia, G, Bernocchi, P, Di Lisa, F & Visioli, O 1993, 'Mitochondrial energy production and cation control in myocardial ischaemia and reperfusion', Basic Research in Cardiology, vol. 88, no. 5, pp. 495-512. https://doi.org/10.1007/BF00795415
Ferrari, R. ; Pedersini, P. ; Bongrazio, M. ; Gaia, G. ; Bernocchi, P. ; Di Lisa, F. ; Visioli, O. / Mitochondrial energy production and cation control in myocardial ischaemia and reperfusion. In: Basic Research in Cardiology. 1993 ; Vol. 88, No. 5. pp. 495-512.
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