PXD070718 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| 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 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-11-14 00:06:23 | ID requested | |
| ⏵ 1 | 2026-01-08 04:14:49 | announced | |
Publication List
Keyword List
| submitter keyword: Ferroptosis |
| Metallothionein |
| Zinc |
| Glutathione |
| Reactive oxygen species (ROS) |
| FBXL5 |
Contact List
| 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 | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD070718
- Label: PRIDE project
- Name: Zinc–MTF1–Metallothionein axis plays critical roles in the defense against ferroptosis in human cells
