Mitochondrial Calcium Overload Plays a Causal Role in Oxidative Stress in the Failing Heart
Haikel Dridi,
Gaetano Santulli,
Laith Bahlouli,
Marco C. Miotto,
Gunnar Weninger,
Andrew R. Marks
Affiliations
Haikel Dridi
Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University Vagelos College of Physicians & Surgeons, New York, NY 10032, USA
Gaetano Santulli
Department of Medicine, Division of Cardiology, Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, New York, NY 10461, USA
Laith Bahlouli
Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University Vagelos College of Physicians & Surgeons, New York, NY 10032, USA
Marco C. Miotto
Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University Vagelos College of Physicians & Surgeons, New York, NY 10032, USA
Gunnar Weninger
Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University Vagelos College of Physicians & Surgeons, New York, NY 10032, USA
Andrew R. Marks
Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University Vagelos College of Physicians & Surgeons, New York, NY 10032, USA
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.
