SR and mitochondria: Calcium cross-talk between kissing cousins

Gerald W. Dorn, Christoph Maack

Research output: Contribution to journalReview articlepeer-review

84 Scopus citations

Abstract

The processes of excitation-contraction coupling in cardiac myocytes require enormous amounts of energy in the form of ATP, which is produced by oxidative phosphorylation in mitochondria. Due to the constantly varying workloads of the heart, efficient matching of energy supply to demand is a requisite for proper heart function. Ca2+ is taken up by mitochondria via the mitochondrial Ca2+ uniporter (MCU) where it stimulates key dehydrogenases of the Krebs cycle to match regeneration of NADH to its oxidation by the respiratory chain. The kinetics of mitochondrial Ca2+ uptake, however, remain controversial due to the low Ca2+ sensitivity of the MCU. Here, we review the evidence for the existence of a "mitochondrial Ca2+ microdomain", in which the close association of the sarcoplasmic reticulum (SR) to mitochondria provides "hot spots" of very high Ca2+ concentrations in the vicinity of mitochondria, sufficient to overcome the low Ca2+ affinity of the MCU. Mitofusins 1 and 2 play redundant roles in regulating mitochondrial dynamics by controlling fusion of mitochondria with each other. Recent work revealed a unique role for mitofusin 2 in tethering mitochondria to the sarco-/endoplasmic reticulum in various cell types, including cardiac myocytes. Disruption of SR-mitochondrial Ca2+ cross talk in heart failure through spatial and ionic alterations may give rise to energetic deficit and oxidative stress, two factors believed to play causal roles in the progression of the disease. On the other hand, excessive mitochondrial Ca2+ uptake can trigger programmed necrosis, substantiating the ambiguity of the close interplay between these cousin organelles in health and disease. This article is part of a Special Issue entitled "Focus on Cardiac Metabolism".

Original languageEnglish
Pages (from-to)42-49
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume55
Issue number1
DOIs
StatePublished - Feb 2013

Keywords

  • Calcium microdomain
  • Excitation-contraction coupling
  • Fission
  • Fusion
  • Mitochondrial energetics
  • Mitofusin

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