%0 Journal Article
%T Mitochondrial Calcium Overload Plays a Causal Role in Oxidative Stress in the Failing Heart.
%A Dridi H
%A Santulli G
%A Bahlouli L
%A Miotto MC
%A Weninger G
%A Marks AR
%J Biomolecules
%V 13
%N 9
%D 2023 09 19
%M 37759809
%F 6.064
%R 10.3390/biom13091409
%X 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.