The Physiological and Pathological Roles of Mitochondrial Calcium Uptake in Heart

Calcium ion (Ca²⁺) plays a critical role in the cardiac mitochondria function. Ca²⁺ entering the mitochondria is necessary for ATP production and the contractile activity of cardiomyocytes. However, excessive Ca²⁺ in the mitochondria results in mitochondrial dysfunction and cell death. Mitochondria maintain Ca²⁺ homeostasis in normal cardiomyocytes through a comprehensive regulatory mechanism by controlling the uptake and release of Ca²⁺ in response to the cellular demand. Understanding the mechanism of modulating mitochondrial Ca²⁺ homeostasis in the cardiomyocyte could bring new insights into the pathogenesis of cardiac disease and help developing the strategy to prevent the heart from damage at an early stage. In this review, we summarized the latest findings in the studies on the cardiac mitochondrial Ca²⁺ homeostasis, focusing on the regulation of mitochondrial calcium uptake, which acts as a double-edged sword in the cardiac function. Specifically, we discussed the dual roles of mitochondrial Ca²⁺ in mitochondrial activity and the impact on cardiac function, the molecular basis and regulatory mechanisms, and the potential future research interest.