Abstract
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(2+)) handling, mitochondrial Ca(2+) overload, and oxidative stress. In cardiomyocytes, Ca(2+) 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(2+) uptake and the molecular pathways involved in the regulation of increased mitochondrial Ca(2+) 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(2+) handling in heart failure and the potential therapeutic strategies.