PXD023882

PXD023882 is an original dataset announced via ProteomeXchange.

Title	Proteomic analysis of U2OS cells treated with the dihydroorotate dehydrogenase (DHODH) inhibitor Brequinar
Description	The mitochondrial respiratory chain assembles into higher order complexes termed supercomplexes (SCs) under certain physiological or metabolic stimuli. A small molecule screen developed by the lab identified DHODH inhibitors as potent activators of SC assembly in cancer cells. To investigate the proteomic regulation of SCs under nucleotide deficiency, we treated U2OS cells for 48 hours with Brequinar (500 nM). Proteomic analysis highlighted strong signatures of respiratory chain subunit abundance and peroxisomal-derived ether phospholipid synthesis enzymes. Bypassing DHODH inhibition through uridine supplementation prevented these alterations. These findings establish a coordinated cellular response to reduced nucleotide pools that stimulates ether phospholipid synthesis and respiratory chain supra-assembly.
HostingRepository	PRIDE
AnnounceDate	2022-02-16
AnnouncementXML	Submission_2022-02-16_14:07:06.801.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	mark Jedrychowski
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-29 04:28:13	ID requested
⏵ 1	2022-02-16 14:07:07	announced

Bennett CF, O'Malley KE, Perry EA, Balsa E, Latorre-Muro P, Riley CL, Luo C, Jedrychowski M, Gygi SP, Puigserver P, Peroxisomal-derived ether phospholipids link nucleotides to respirasome assembly. Nat Chem Biol, 17(6):703-710(2021) [pubmed]

ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP), Diabetes (B/D-HPP), Human Proteome Project

submitter keyword: Nucleotides, pyrimidines, dihydroorotate dehydrogenase, mitochondria, respirasome, supercomplexes

Pere Puigserver
contact affiliation	Dana Farber Cancer Institute Boston, MA USA
contact email	Pere_Puigserver@dfci.harvard.edu
lab head
mark Jedrychowski
contact affiliation	Harvard Medical School
contact email	mark_jedrychowski@hms.harvard.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/2022/02/PXD023882

PRIDE project URI

• PRIDE
  1. PXD023882
     1. Label: PRIDE project
     2. Name: Proteomic analysis of U2OS cells treated with the dihydroorotate dehydrogenase (DHODH) inhibitor Brequinar