Review Article

Mitochondrial Ca2+ regulation in the etiology of heart failure: physiological and pathophysiological implications

Authors: Hai-xia Xu1,2, Su-mei Cui3,4, Ying-mei Zhang1, Jun Ren1,5
1 Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China
2 Department of Cardiology, Affiliated Hospital of Nantong University, Nantong 226001, China
3 Department of Emergency Medicine, Qilu Hospital of Shandong University, Ji-nan 250012, China
4 Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Ji-nan 250012, China
5 University of Wyoming College of Health Sciences, Laramie, WY 82071, USA
Correspondence to: Ying-mei Zhang: zhangym197951@126.com, Jun Ren: jren_aldh2@outlook.com,
DOI: 10.1038/s41401-020-0476-5
Received: 27 April 2020
Accepted: 6 July 2020
Advance online: 21 July 2020

Abstract

Heart failure (HF) represents one of the leading causes of cardiovascular diseases with high rates of hospitalization, morbidity and mortality worldwide. Ample evidence has consolidated a crucial role for mitochondrial injury in the progression of HF. It is well established that mitochondrial Ca2+ participates in the regulation of a wide variety of biological processes, including oxidative phosphorylation, ATP synthesis, reactive oxygen species (ROS) generation, mitochondrial dynamics and mitophagy. Nonetheless, mitochondrial Ca2+ overload stimulates mitochondrial permeability transition pore (mPTP) opening and mitochondrial swelling, resulting in mitochondrial injury, apoptosis, cardiac remodeling, and ultimately development of HF. Moreover, mitochondria possess a series of Ca2+ transport influx and efflux channels, to buffer Ca2+ in the cytoplasm. Interaction at mitochondria-associated endoplasmic reticulum membranes (MAMs) may also participate in the regulation of mitochondrial Ca2+ homeostasis and plays an essential role in the progression of HF. Here, we provide an overview of regulation of mitochondrial Ca2+ homeostasis in maintenance of cardiac function, in an effort to identify novel therapeutic strategies for the management of HF.
Keywords: heart failure; mitochondrial Ca2+ homeostasis; mitochondrial Ca2+ transport; MAMs; ATP synthesis ROS production; myocardial apoptosis

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