PXD020551

PXD020551 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-23 23:38:47	ID requested
⏵ 1	2021-09-09 00:31:20	announced

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]

submitter keyword: mitochodria, quantitative proteomics, pulmonary vasoconstriction, Antimycin A

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD020551

PRIDE project URI

• PRIDE
  1. PXD020551
     1. Label: PRIDE project
     2. Name: Effect of mitochEffect of mitochondrial complex III chronic inhibition on mitochondrial proteomic landscapeondrial complex III chronic inhibition on mitochondrial proteomic landscape