Mitochondrial calcium uniporter complex: An emerging therapeutic target for cardiovascular diseases (Review)

Abstract

Cardiovascular disease (CVD) is currently a major factor affecting human physical and mental health. In recent years, the relationship between intracellular Ca²⁺ and CVD has been extensively studied. Ca²⁺ movement across the mitochondrial inner membrane plays a vital role as an intracellular messenger, regulating energy metabolism and calcium homeostasis. It is also involved in pathological processes such as cardiomyocyte apoptosis, hypertrophy and fibrosis in CVD. The selective mitochondrial calcium uniporter complex (MCU complex) located in the inner membrane is essential for mitochondrial Ca²⁺ uptake. Therefore, the MCU complex is a potential therapeutic target for CVD. In this review, recent research progress on the pathophysiological mechanisms and therapeutic potential of the MCU complex in various CVDs was summarized, including myocardial ischemia‑reperfusion injury, pulmonary arterial hypertension, other peripheral vascular diseases, myocardial remodeling and arrhythmias. This review contributes to a deeper understanding of these mechanisms at the molecular level and highlights potential intervention targets for CVD treatment in clinical practice.

Keywords: cardiovascular diseases; emerging; mitochondrial calcium uniporter complex; therapeutic target.

Figure 1

Role of the MCU complex in cardiovascular diseases. The core of the MCU channel consists of the transmembrane proteins MCU, MCUb and EMRE. Together, the MCU isoforms assemble into a pentamer (or tetramer) structure in the inner mitochondrial membrane, forming a Ca²⁺-conducting pore. The activity of this pore is regulated by members of the MICU. The impact of the MCU complex on cardiovascular diseases is illustrated, with '+; indicating promoting effects and '-' indicating inhibitory effects. MCU, mitochondrial Ca²⁺ uniporter; MICU, mitochondrial Ca²⁺ uptake protein family; I/R, ischemia/reperfusion; EMRE, essential MCU regulator; PAH, pulmonary arterial hypertension; HF, heart failure; AF, atrial fibrillation; PVT, polymorphic ventricular tachycardia.

Figure 2

The impact of the MCU complex on cardiovascular diseases can induce either cell proliferation or apoptosis. These effects can be alleviated through various interventions, such as Ru360, NecroX-5, DS16570511 and certain traditional Chinese herbs. MCU, mitochondrial Ca²⁺ uniporter.