PXD060069-1

PXD060069 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Oxidation of Retromer Complex controls Mitochondrial Translation
Description	Reactive oxygen species (ROS) underlie human pathologies including cancer and neurodegeneration. The mitochondrial electron transport chain is appreciated as a key regulator of ROS stoichiometry in cells. However, the pathways that sense and regulate ROS levels more broadly remain to be fully elucidated. Here, systematic base-editor and computational screens identify VPS35, a member of the Retromer trafficking complex, as a cytosolic ROS sensor. Mechanistically, we find that VPS35 C653/C673 regulates compartmentalized mitochondrial translation by disrupting the plasma membrane localization of SLC7A1, leading to dramatic resistance against ROS-generating anti-cancer agents including cisplatin. Our study describes the regulation of compartmentalized translation and cellular ROS homeostasis by a single amino acid within vesicular trafficking machinery, supporting the long-standing hypothesis that mitochondrial ROS is implicated in cisplatin resistance. We anticipate that the approaches employed herein may template a generalizable method for the identification of functional ROS targets and sensors under various biological contexts.
HostingRepository	MassIVE
AnnounceDate	2025-01-22
AnnouncementXML	Submission_2025-01-22_12:10:48.660.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Harrison Chong
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	unknown modification
Instrument	Orbitrap Eclipse

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-22 11:55:05	ID requested
⏵ 1	2025-01-22 12:10:49	announced

Publication List

no publication

no publication

Keyword List

submitter keyword: K562, Plasma Membrane, Anti-cancer Agents, DatasetType:Proteomics

submitter keyword: K562, Plasma Membrane, Anti-cancer Agents, DatasetType:Proteomics

Contact List

Liron Bar-Peled
contact affiliation	Massachusetts General Hospital Cancer Center
contact email	lbar-peled@mgh.harvard.edu
lab head
Harrison Chong
contact affiliation	Massachusetts General Hospital Cancer Center
contact email	hbchong@mgh.harvard.edu
dataset submitter

Full Dataset Link List

MassIVE dataset URI
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://massive.ucsd.edu/v09/MSV000096912/

MassIVE dataset URI

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://massive.ucsd.edu/v09/MSV000096912/