Related Experiment Video
Updated: May 13, 2026
04:01
Revealing the Ferroptotic Phenotype of Medulloblastoma
Published on: March 15, 2024
Rv1983 promotes mycobacterial dissemination by triggering ferroptosis through GPX4 ubiquitination
Zilu Qu1,2, Yuanyuan Zhou3, Qinzhen Cai4
1Hubei Province and Key Laboratory of Skin Infection and Immunity, Wuhan No. 1 Hospital, Wuhan, 430022, China.
Cellular & Molecular Biology Letters
|May 12, 2026
Summary
Mycobacterium tuberculosis protein Rv1983 induces macrophage ferroptosis by degrading GPX4, promoting bacterial spread. Targeting this Rv1983-TRIM25-GPX4 pathway offers a potential therapeutic strategy for tuberculosis.
Area of Science:
- Cell Biology
- Immunology
- Microbiology
Background:
- Ferroptosis, an iron-dependent cell death, is linked to tuberculosis pathogenesis.
- The role of Mycobacterium tuberculosis (Mtb) proteins in macrophage ferroptosis remains unclear.
Purpose of the Study:
- Screen Mtb RD region-encoded proteins for macrophage ferroptosis induction.
- Elucidate the molecular mechanisms of Mtb-mediated ferroptosis.
Main Methods:
- Screened Mtb RD proteins for cytotoxic activity, identifying Rv1983.
- Determined cell death modality using flow cytometry and western blotting.
- Assessed Mtb dissemination in vitro and in vivo using Rv1983-knockout strains.
Main Results:
- Rv1983 (PE_PGRS35) induces macrophage ferroptosis by degrading GPX4 via TRIM25.
- Rv1983 binds TRIM25, leading to GPX4 ubiquitination and degradation.
- Rv1983 deficiency suppressed Mtb dissemination in vitro and in vivo.
Conclusions:
- Rv1983 is a key Mtb effector promoting ferroptosis and dissemination.
- The Rv1983-TRIM25-GPX4 axis is crucial for Mtb-induced ferroptosis.
- Targeting this pathway presents a potential therapeutic strategy for tuberculosis.
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