Abstract

Cardiovascular diseases (CVDs), the leading cause of death worldwide, share in common mitochondrial dysfunction, in specific a dysregulation of Ca2+ uptake dynamics through the mitochondrial Ca2+ uniporter (MCU) complex. In particular, Ca2+ uptake regulates the mitochondrial ATP production, mitochondrial dynamics, oxidative stress, and cell death. Therefore, modulating the activity of the MCU complex to regulate Ca2+ uptake, has been suggested as a potential therapeutic approach for the treatment of CVDs. Here, the role and implications of the MCU complex in CVDs are presented, followed by a review of the evidence for MCU complex modulation, genetically and pharmacologically. While most approaches have aimed within the MCU complex for the modulation of the Ca2+ pore channel, the MCU subunit, its intra- and extra- mitochondrial implications, including Ca2+ dynamics, oxidative stress, post-translational modifications, and its repercussions in the cardiac function, highlight that targeting the MCU complex has the translational potential for novel CVDs therapeutics.