PXD020551 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Effect of mitochEffect of mitochondrial complex III chronic inhibition on mitochondrial proteomic landscapeondrial complex III chronic inhibition on mitochondrial proteomic landscape |
Description | The mitochondria play a vital role in controlling cell metabolism and regulating crucial cellular outcomes. We previously demonstrated that chronic inhibition of the mitochondrial complex III in rats by Antimycin A (AA) induced pulmonary vasoconstriction. On the metabolic level, AA-induced mitochondrial dysfunction resulted in a glycolytic shift that was reported as the primary contributor to pulmonary hypertension pathogenesis. However, the regulatory proteins driving this metabolic shift with complex III inhibition are yet to be explored. Therefore, to delineate the mechanisms, we followed the rat lung mitochondrial proteomics. Rats treated with the complex III inhibitor, Antimycin-A for up to 24 days, showed a disturbed mitochondrial proteome with significant changes in 28 proteins (p<0.05). We observe a time-dependent decrease in the expression of key proteins that regulate fatty acid oxidation, the tricarboxylic acid cycle, electron transport chain, and amino acid metabolism, indicating diminished mitochondrial function. We also found a significant dysregulation in proteins that control protein import, and the clearance and detoxification of oxidatively damaged peptides via proteolysis and mitophagy. This could lead to the onset of mitochondrial toxicity due to the misfolded protein's stress. We conclude that chronic inhibition of the mitochondrial complex III attenuates mitochondrial function by disruption of global mitochondrial metabolism. This potentially aggravates cellular proliferation by initiating a glycolytic switch and thereby leading to pulmonary hypertension. |
HostingRepository | PRIDE |
AnnounceDate | 2021-09-09 |
AnnouncementXML | Submission_2021-09-09_00:31:19.853.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD020551 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Paul Langlais |
SpeciesList | scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116; |
ModificationList | phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-07-23 23:38:47 | ID requested | |
⏵ 1 | 2021-09-09 00:31:20 | announced | |
Publication List
James J, Valuparampil Varghese M, Vasilyev M, Langlais PR, Tofovic SP, Rafikova O, Rafikov R, Complex III Inhibition-Induced Pulmonary Hypertension Affects the Mitochondrial Proteomic Landscape. Int J Mol Sci, 21(16):(2020) [pubmed] |
Keyword List
submitter keyword: mitochodria, quantitative proteomics, pulmonary vasoconstriction, Antimycin A |
Contact List
Ruslan Rafikov |
contact affiliation | University of Arizona College of Medicine, Department of Medicine, Division of Endocrinology |
contact email | ruslanrafikov@deptofmed.arizona.edu |
lab head | |
Paul Langlais |
contact affiliation | University of Arizona |
contact email | langlais@deptofmed.arizona.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD020551
- Label: PRIDE project
- Name: Effect of mitochEffect of mitochondrial complex III chronic inhibition on mitochondrial proteomic landscapeondrial complex III chronic inhibition on mitochondrial proteomic landscape