PXD029890

PXD029890 is an original dataset announced via ProteomeXchange.

Title	MICU3 Plays an Important Role in Cardiovascular Function
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.
HostingRepository	MassIVE
AnnounceDate	2021-11-29
AnnouncementXML	Submission_2021-11-29_10:38:36.761.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Angel Aponte
SpeciesList	scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-23 20:13:11	ID requested
⏵ 1	2021-11-29 10:38:37	announced

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, 127(12):1571-1573(2020) [pubmed]

submitter keyword: TMT

Elizabeth Murphy, PhD
contact affiliation	Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health
contact email	murphy1@nhlbi.nih.gov
lab head
Angel Aponte
contact affiliation	NIH/NHLBI
contact email	apontea@nhlbi.nih.gov
dataset submitter

MassIVE dataset URI

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