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 (Ca2+) handling, mitochondrial Ca2+ overload, and oxidative stress. In cardiomyocytes, Ca2+ 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 Ca2+ uptake and the molecular pathways involved in the regulation of increased mitochondrial Ca2+ 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 Ca2+ handling in heart failure and the potential therapeutic strategies.

Automated summary

Heart failure is a global health challenge characterized by defective calcium handling, mitochondrial calcium overload, and oxidative stress. Calcium not only regulates contraction in cardiomyocytes, but also affects mitochondrial metabolism and oxidative stress signaling. Understanding the mechanisms of mitochondrial calcium uptake and the regulation of increased calcium influx is crucial for identifying therapeutic targets for heart failure.