PXD070718

PXD070718 is an original dataset announced via ProteomeXchange.

Title	Zinc–MTF1–Metallothionein axis plays critical roles in the defense against ferroptosis in human cells
Description	Ferroptosis, an iron-dependent form of regulated cell death characterized by the accumulation of lipid hydroperoxides, has attracted intense attention for its potential clinical applications. Ferroptosis is governed by redox reactions, yet the factors regulating this process, as well as their relationship with the central mediator glutathione (GSH), warrant further investigation. Metallothioneins (MTs), cysteine-rich proteins that play central roles in zinc storage and homeostasis, comprise eleven isoforms in humans. This isoform multiplicity complicates the functional analysis of human MTs, making it difficult to generate knockout cell lines and elucidate their precise roles in biological processes including ferroptosis. Here, we established MTs-knockout human cell lines and demonstrated that MTs protect against ferroptosis induced by iron overload or GSH depletion, primarily by cooperatively suppressing reactive oxygen species (ROS) production alongside GSH. Zinc enhances this protective effect by inducing MTs expression via activation of metal-responsive transcription factor 1 (MTF1). Importantly, this protective function is conserved across different types of human cells, and MTs expression levels may contribute to cell-type-specific susceptibility to ferroptosis. These findings highlight zinc–MTF1–MT axis as a critical regulatory pathway that operates in parallel with, and complements, the GSH/GPX4 system in the control of ferroptosis and may provide a promising target for ferroptosis-directed therapeutic strategies.
HostingRepository	PRIDE
AnnounceDate	2026-01-08
AnnouncementXML	Submission_2026-01-08_04:14:48.959.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yuki Maeda
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	ZenoTOF 7600

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-14 00:06:23	ID requested
⏵ 1	2026-01-08 04:14:49	announced

10.1016/J.FREERADBIOMED.2026.01.008;

submitter keyword: Ferroptosis

Metallothionein

Zinc

Glutathione

Reactive oxygen species (ROS)

FBXL5

Yasuo Uchida
contact affiliation	Graduate school of Biomedical and Health Sciences, Hiroshima University
contact email	yuchida@hiroshima-u.ac.jp
lab head
Yuki Maeda
contact affiliation	Hiroshima University
contact email	yuki16270102@gmail.com
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/2026/01/PXD070718

PRIDE project URI

• PRIDE
  1. PXD070718
     1. Label: PRIDE project
     2. Name: Zinc–MTF1–Metallothionein axis plays critical roles in the defense against ferroptosis in human cells