Mitochondrial and Sarcoplasmic Reticulum Interconnection in Cardiac Arrhythmia

Abstract

Ca²⁺ plays a pivotal role in mitochondrial energy production, contraction, and apoptosis. Mitochondrial Ca²⁺-targeted fluorescent probes have demonstrated that mitochondria Ca²⁺ transients are synchronized with Ca²⁺ fluxes occurring in the sarcoplasmic reticulum (SR). The presence of specialized proteins tethering SR to mitochondria ensures the local Ca²⁺ flux between these organelles. Furthermore, communication between SR and mitochondria impacts their functionality in a bidirectional manner. Mitochondrial Ca²⁺ uptake through the mitochondrial Ca²⁺ 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 Ca²⁺-handling proteins, which ensures that mitochondria receive an adequate supply of Ca²⁺. Recent evidence suggests that altered SR Ca²⁺ proteins, such as ryanodine receptors and the sarco/endoplasmic reticulum Ca²⁺ 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.

Keywords: arrhythmia; calcium; heart failure; ischemia/reperfusion injury; mitochondria; sarcoplasmic reticulum.