@article{Chen2026, 
author = {Jie-Yu Chen and Ya-Fen Huang and Yu Hong},
title = {Mitochondrial outer membrane protein FUNDC2 contributes to ferroptosis as a potential upstream regulator in retinitis pigmentosa},
year = {2026},
journal = {International Journal of Ophthalmology},
volume = {19},
number = {9},
pages = {1667-1675},
keywords = {retinitis pigmentosa, ferroptosis, FUNDC2, retinal pigment epithelium, sodium iodate},
url = {https://www.sciopen.com/article/10.18240/ijo.2026.09.02},
doi = {10.18240/ijo.2026.09.02},
abstract = {AIMTo 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.METHODSUnbiased 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.RESULTSProteomic 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.CONCLUSIONThese 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.}
}