Targeting the mitochondrial Ca 2+ uniporter complex in cardiovascular disease

Cardiovascular diseases (CVDs), the leading cause of death worldwide, share in common mitochondrial dysfunction, in specific a dysregulation of Ca uptake dynamics through the mitochondrial Ca uniporter (MCU) complex. In particular, Ca uptake regulates the mitochondrial ATP production, mitochondrial...

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Bibliographic Details
Published in:Acta Physiologica 2023-04, Vol.237 (4), p.e13946
Main Authors: Lozano, Omar, Marcos, Patricio, Salazar-Ramirez, Felipe de Jesús, Lázaro-Alfaro, Anay F, Sobrevia, Luis, García-Rivas, Gerardo
Format: Article
Language:English
Subjects:
Calcium - metabolism
Calcium Channels - genetics
Cardiovascular Diseases - drug therapy
Cardiovascular Diseases - metabolism
Humans
Mitochondria - metabolism
Oxidative Stress
Protein Processing, Post-Translational
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Summary:Cardiovascular diseases (CVDs), the leading cause of death worldwide, share in common mitochondrial dysfunction, in specific a dysregulation of Ca uptake dynamics through the mitochondrial Ca uniporter (MCU) complex. In particular, Ca uptake regulates the mitochondrial ATP production, mitochondrial dynamics, oxidative stress, and cell death. Therefore, modulating the activity of the MCU complex to regulate Ca 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 Ca pore channel, the MCU subunit, its intra- and extra- mitochondrial implications, including Ca 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.
ISSN:1748-1708
1748-1716
DOI:10.1111/apha.13946