MassIVE MSV000088439

Complete Public PXD029890

MICU3 Plays an Important Role in Cardiovascular Function

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Description

Mitochondrial calcium regulates bioenergetics but also serves as a trigger for cell death.1 With a sustained increase in catecholamine or a large increase in cytosolic calcium as occurs with ischemia, mitochondrial calcium can rise to high levels, leading to activation of the mitochondrial permeability transition pore, thus initiating cell death.1 Calcium uptake into mitochondria occurs via the MCU (mitochondrial calcium uniporter), which is regulated by 3 EF (EF hand protein) hand proteins, MICU (mitochondrial calcium uptake) 1, 2, and 3.2 MICU1/MCU ratios vary in different tissues,3 and alterations in substrate flux have been shown to regulate MICU1 levels altering MCU-mediated calcium uptake.4 MICU3 has generally been thought to function primarily in neuronal tissue where it is highly expressed and thus has been largely ignored in other tissues such as the heart. We performed quantitative proteomics using Tandem mass tag labeling coupled to liquid chromatography and tandem mass spectrometry to analyze MCU and MCU regulators in cardiac and hepatic mitochondria (Figure [A]). Normalizing MICU levels to MCU in heart and liver mitochondria, we found that the MICU1/MCU ratio was 0.75 in liver and 0.25 in heart, which is consistent with previous studies3; however, the MICU3/MCU ratio in heart is >3-fold higher than that found in liver. To confirm that the MICU3 we observed in heart mitochondria was not due to contamination by mitochondria from nerve tissue in heart, we isolated cardiomyocytes and compared the ratio of MICU3 to MCU in cardiomyocytes and heart mitochondria and found similar ratios (Figure [B]). These data suggest that MICU3 might play a role in regulating MCU in heart. [doi:10.25345/C50K3H] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: TMT

Contact

Principal Investigators:
(in alphabetical order) 		Elizabeth Murphy, PhD, Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, USA
Submitting User: aponte

Publications

Puente BN, Sun J, Parks RJ, Fergusson MM, Liu C, Springer DA, Aponte AM, Liu JC, Murphy E.
MICU3 Plays an Important Role in Cardiovascular Function.
Circ Res. 2020 Dec 4;127(12):1571-1573. doi: 10.1161/CIRCRESAHA.120.317177.

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