Mitochondrial Ca Homeostasis: Emerging Roles and Clinical Significance in Cardiac Remodeling.

Mitochondria are the sites of oxidative metabolism in eukaryotes where the metabolites of sugars, fats, and amino acids are oxidized to harvest energy. Notably, mitochondria store Ca and work in synergy with organelles such as the endoplasmic reticulum and extracellular matrix to control the dynamic balance of Ca concentration in cells. Mitochondria are the vital organelles in heart tissue. Mitochondrial Ca homeostasis is particularly important for maintaining the physiological and pathological mechanisms of the heart. Mitochondrial Ca homeostasis plays a key role in the regulation of cardiac energy metabolism, mechanisms of death, oxygen free radical production, and autophagy. The imbalance of mitochondrial Ca balance is closely associated with cardiac remodeling. The mitochondrial Ca uniporter (mtCU) protein complex is responsible for the uptake and release of mitochondrial Ca and regulation of Ca homeostasis in mitochondria and consequently, in cells. This review summarizes the mechanisms of mitochondrial Ca homeostasis in physiological and pathological cardiac remodeling and the regulatory effects of the mitochondrial calcium regulatory complex on cardiac energy metabolism, cell death, and autophagy, and also provides the theoretical basis for mitochondrial Ca as a novel target for the treatment of cardiovascular diseases.