The SR-mitochondria interaction: A new player in cardiac pathophysiology

Marisol Ruiz-Meana, Celia Fernandez-Sanz, David Garcia-Dorado

Research output: Contribution to journalReview articleResearchpeer-review

70 Citations (Scopus)

Abstract

Mitochondria are essential for energy supply and cell signalling and may be triggers and effectors of cell death. Mitochondrial respiration is tightly controlled by the matrix Ca2+ concentration, which is beat-to-beat regulated by uptake and release mainly through the mitochondrial Ca2+ uniporter and Na+/Ca2+ exchanger, respectively. Recent studies demonstrate that mitochondrial Ca2+ uptake is more dependent on anatomo-functional microdomains established with the sarcoplasmic reticulum (SR) than on cytosolic Ca2+. This privileged communication between SR and mitochondria is not restricted to Ca2+ but may involve ATP and reactive oxygen species, which has important implications in cardiac pathophysiology. The disruption of the SR-mitochondria interaction caused by cell remodelling has been implicated in the deterioration of excitation-contraction coupling of the failing heart. The SR-mitochondria interplay has been suggested to be involved in the depressed Ca2+ transients and mitochondrial dysfunction observed in diabetic hearts as well as in the genesis of certain arrhythmias, and it may play an important role in myocardial reperfusion injury. During reperfusion, re-energization in the presence of cytosolic Ca2+ overload results in SR-driven Ca 2+ oscillations that may promote mitochondrial permeability transition (MPT). The relationship between MPT and Ca2+ oscillations is bidirectional, as recent data show that the induction of MPT in Ca 2+-overloaded cardiomyocytes may result in mitochondrial Ca 2+ release that aggravates Ca2+ handling and favours hypercontracture. A more complete characterization of the structural arrangements responsible for SR-mitochondria interplay will allow better understanding of cardiac (patho)physiology but also, and no less important, should serve as a basis for the development of new treatments for cardiac diseases. © The Author 2010.
Original languageEnglish
Pages (from-to)30-39
JournalCardiovascular Research
Volume88
Issue number1
DOIs
Publication statusPublished - 1 Oct 2010

Keywords

  • Ageing
  • Calcium microdomains
  • Diabetes
  • Heart failure
  • Ischaemia-reperfusion

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