PXD050739-1

PXD050739 is an original dataset announced via ProteomeXchange.

Title	Regulation of mitochondrial oxidative phosphorylation and venetoclax efficacy in AML via COX4I1
Description	Cell signaling pathways are enriched for biological processes crucial for cellular communication, response to external stimuli, and metabolism. Here, we conducted a cell signaling-focused CRISPR screen and identified cytochrome c oxidase subunit 4I1 (COX4I1) as a novel vulnerability in acute myeloid leukemia (AML). Depletion of COX4I1 hindered leukemia cell proliferation and impacted in vivo AML progression. Mechanistically, loss of COX4I1 induced mitochondrial stress and ferroptosis, disrupting mitochondrial ultrastructure and oxidative phosphorylation. CRISPR gene tiling scans, coupled with mitochondrial proteomics, dissected critical regions within COX4I1 essential for leukemia cell survival, providing detailed insights into the mitochondrial Complex IV assembly network. Furthermore, COX4I1 depletion or pharmacological inhibition of Complex IV (using chlorpromazine) synergized with venetoclax, providing a promising avenue for improved leukemia therapy. Our study highlights COX4I1 as a critical mitochondrial checkpoint, offering insights into its functional significance and potential clinical implications.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_13:18:15.355.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ting-Yu Wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-18 16:26:51	ID requested
⏵ 1	2025-05-06 13:18:16	announced

10.1002/advs.202404620;

Zhang L, Zhang H, Wang TY, Li M, Chan AKN, Kang H, Foong LC, Liu Q, Pokharel SP, Mattson NM, Singh P, Elsayed Z, Kuang B, Wang X, Rosen ST, Chen J, Yang L, Chou TF, Su R, Chen CD, Nuclear Control of Mitochondrial Homeostasis and Venetoclax Efficacy in AML via COX4I1. Adv Sci (Weinh), 12(6):e2404620(2025) [pubmed]

submitter keyword: leukemia,COX4I1, mitochondria

Tsui-Fen Chou
contact affiliation	Proteome Exploration Laboratory, California Institute of Technology, Pasadena, CA, USA
contact email	tfchou@caltech.edu
lab head
Ting-Yu Wang
contact affiliation	Caltech
contact email	tywang@caltech.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/2025/05/PXD050739

PRIDE project URI

• PRIDE
  1. PXD050739
     1. Label: PRIDE project
     2. Name: Regulation of mitochondrial oxidative phosphorylation and venetoclax efficacy in AML via COX4I1