Mitochondrial and Sarcoplasmic Reticulum Interconnection in Cardiac Arrhythmia
Felipe Salazar‐Ramírez, Roberto Ramos‐Mondragón, Gerardo García‐Rivas
Abstract
Ca 2+ plays a pivotal role in mitochondrial energy production, contraction, and apoptosis. Mitochondrial Ca 2+ -targeted fluorescent probes have demonstrated that mitochondria Ca 2+ transients are synchronized with Ca 2+ fluxes occurring in the sarcoplasmic reticulum (SR). The presence of specialized proteins tethering SR to mitochondria ensures the local Ca 2+ flux between these organelles. Furthermore, communication between SR and mitochondria impacts their functionality in a bidirectional manner. Mitochondrial Ca 2+ uptake through the mitochondrial Ca 2+ uniplex is essential for ATP production and controlled reactive oxygen species levels for proper cellular signaling. Conversely, mitochondrial ATP ensures the proper functioning of SR Ca 2+ -handling proteins, which ensures that mitochondria receive an adequate supply of Ca 2+ . Recent evidence suggests that altered SR Ca 2+ proteins, such as ryanodine receptors and the sarco/endoplasmic reticulum Ca 2+ ATPase pump, play an important role in maintaining proper cardiac membrane excitability, which may be initiated and potentiated when mitochondria are dysfunctional. This recognized mitochondrial role offers the opportunity to develop new therapeutic approaches aimed at preventing cardiac arrhythmias in cardiac disease.