Mitochondrial Calcium Overload Plays a Causal Role in Oxidative Stress in the Failing Heart.

Heart failure is a serious global health challenge, affecting more than 6.2 million people in the United States and is projected to reach over 8 million by 2030. Independent of etiology, failing hearts share common features, including defective calcium (Ca) handling, mitochondrial Ca overload, and oxidative stress. In cardiomyocytes, Ca not only regulates excitation-contraction coupling, but also mitochondrial metabolism and oxidative stress signaling, thereby controlling the function and actual destiny of the cell. Understanding the mechanisms of mitochondrial Ca uptake and the molecular pathways involved in the regulation of increased mitochondrial Ca influx is an ongoing challenge in order to identify novel therapeutic targets to alleviate the burden of heart failure. In this review, we discuss the mechanisms underlying altered mitochondrial Ca handling in heart failure and the potential therapeutic strategies.