title: Calcium release microdomains and mitochondria.
abstract: The processes of excitation-contraction (EC) coupling consume large amounts of energy that need to be replenished by oxidative phosphorylation in the mitochondria. Since Ca(2+) activates key enzymes of the Krebs cycle in the mitochondrial matrix, it is important to understand the mechanisms and kinetics of mitochondrial Ca(2+) uptake to delineate how in cardiac myocytes, energy supply is efficiently matched to demand. In recent years, the identification of various proteins involved in mitochondrial Ca(2+) signalling and the tethering of mitochondria to the sarcoplasmic reticulum (SR) has considerably advanced the field and supported the concept of a mitochondrial Ca(2+) microdomain, in which Ca(2+) concentrations are high enough to overcome the low Ca(2+) affinity of the principal mitochondrial Ca(2+) uptake mechanism, the Ca(2+) uniporter. Furthermore, defects in EC coupling that occur in heart failure disrupt SR-mitochondrial Ca(2+) crosstalk and may cause energetic deficit and oxidative stress, both factors that are thought to be causally involved in the initiation and progression of the disease.
authors: Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg 66421, Germany.
authors: Michael
authors: M
authors: Kohlhaas
authors: Christoph
authors: C
authors: Maack
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004734:Energy Metabolism; D056966:Excitation Contraction Coupling; D020558:GTP Phosphohydrolases / Q000502:physiology; D006333:Heart Failure / Q000503:physiopathology; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000502:physiology
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D017382:Reactive Oxygen Species; D019831:Sodium-Calcium Exchanger; D017868:Cyclic AMP-Dependent Protein Kinases; D020558:GTP Phosphohydrolases; C470017:Mfn1 protein, human; D002118:Calcium