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Updated: Aug 26, 2026

Revealing the Ferroptotic Phenotype of Medulloblastoma
Published on: March 15, 2024
Mitochondrial outer membrane protein FUNDC2 contributes to ferroptosis as a potential upstream regulator in retinitis
Jie-Yu Chen1, Ya-Fen Huang1, Yu Hong1
1Department of Ophthalmology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian Province, China.
Aim:
To investigate the key role of the mitochondrial outer membrane protein FUN14 domain-containing 2 (FUNDC2) in retinal pigment epithelium (RPE) ferroptosis during retinitis pigmentosa (RP) progression.
Methods:
Unbiased label-free proteomics was employed to identify differentially expressed proteins in the RPE of a sodium iodate (SI)-induced rat model. In vitro experiments were conducted using human retinal pigment epithelial (ARPE)-19 cells. The effects of SI treatment and FUNDC2 knockdown on cell viability and the expression of ferroptosis-protective molecules, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), ferritin heavy chain 1 (FTH1), and solute carrier family 25 member 11 (SLC25A11) were evaluated.
Results:
Proteomic analysis revealed that FUNDC2 was significantly upregulated in the RPE of SI-induced rats. In ARPE-19 cells, SI treatment significantly increased FUNDC2 expression while decreasing the levels of ferroptosis-protective molecules. Functional experiments demonstrated that knocking down FUNDC2 effectively rescued SI-induced loss of cell viability and restored GPX4 expression.
Conclusion:
These findings provide the first evidence that FUNDC2 acts as a potential upstream regulator of RPE ferroptosis in RP, at least partially by negatively regulating GPX4. Consequently, FUNDC2 is a potential therapeutic target for the future treatment of RP.
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