2025/10/31 by Shanice S. Webster · 1 voice
Medicine · Agricultural and Biological Sciences · #Ferroptosis and cancer prognosis #Plant Micronutrient Interactions and Effects #Iron Metabolism and Disorders
paper · pdf · doi:10.1093/plcell/koaf273
openalex publication_date 2025/10/31 · openalex created_date 2025/11/18 · openalex updated_date 2026/07/31
Too much of anything is rarely good. For iron, sufficient amounts are essential to support cellular processes in plants such as photosynthesis and respiration, while excessive levels are toxic, leading to stunted growth, leaf damage, and pathogen proliferation. However, there is emerging evidence that excess iron plays a role in plant defense against pathogens. This defense strategy involves an iron-dependent form of cell death known as ferroptosis that kills infected plant cells to limit pathogen spread. Ferroptosis is well-described in mammals and is distinct from other types of regulated cell death strategies such as apoptosis and autophagy (Yan et al. 2021). During ferroptosis, excess iron induces reactive oxygen species (ROS) production, which triggers the accumulation of lipid peroxides that damage cell membranes. While ferroptosis is emerging as a key immune process in plants, its regulatory mechanisms are not well understood. In recent work, Chenxing Hao and colleagues (Hao et al. 2025) identify a protein in citrus that induces iron uptake, triggers ferroptosis, and increases resistance to citrus canker. The study highlights a complex regulatory network of positive and negative regulation to modulate foliar iron content during infection (see Figure). Proposed model of CmOGD2 regulation by CmZAT10 and CmENO2 under basal conditions and during Xcc infection to tune iron uptake and ferroptosis. Left, CmZAT10 weakly activates CmOGD2 while interaction with CmENO2 restrains it, yielding low scopoletin and basal iron levels. Right, Xcc pthA4 effector disrupts CmOGD2–CmENO2 interaction and elevates CmZAT10, increasing scopoletin levels, which induce iron uptake and ferroptosis. Reprinted from Hao et al. (2025), Figure 7. Citrus canker is caused by the foliar pathogen Xanthomonas citri subsp. citri (Xcc) that infects most commercial varieties of citrus, such as lemon and sweet orange. In previous work, Citron-05 (Citrus medica L.) was identified as the only known resistant citrus germplasm to Xcc. However, the underlying mechanism of Citron-05's resistance remained unknown until now (Fu et al. 2020). Using comparative transcriptomics of Xcc-infected sweet orange and Citron-05, the authors identified CmOGD2 as a candidate resistance gene that is highly expressed in Citron-05 relative to sweet orange. Transgenic overexpression of CmOGD2 in sweet orange increased resistance to Xcc, whereas silencing CmOGD2 in Citron-05 heightened susceptibility. These results highlight CmOGD2 as a promising target for mechanistic studies and resistance improvement. CmOGD2 is homologous to Arabidopsis AtF6'H1, which encodes an enzyme required for biosynthesis of coumarin scopoletin, known to be involved in iron acquisition. To test functional equivalence, CmOGD2 was expressed in E. coli. Upon providing feruloyl CoA—the substrate of F6'H1—scopoletin levels increased, indicating that scopoletin is the direct enzymatic product of CmOGD2. Consistently, Citron-05 plants challenged with Xcc showed increased scopoletin and iron levels. Xcc elicits divergent symptoms in sweet orange and Citron-05. The former produces enlarged hyperplastic lesions while the latter shows discolored necrotic spots indicative of cell death. Surprisingly, both biotypes show a similar increase in ROS during Xcc infection. However, the authors found that ROS accumulates in epidermal cells in sweet orange and mesophyll cells in Citron-05. Given the difference in ROS localization in sweet orange and Citron-05, the authors hypothesized that mesophyll-localized ROS might trigger defense-related programmed cell death and contribute to resistance in Citron-05. Using FSD1 as a marker for ROS production, the authors observed that ROS levels were elevated when Citron-05 was infected with Xcc. This increase in ROS coincided with increased iron levels. Additionally, treatment with chemicals such as diphenyliodonium chloride, which inhibits ROS production, or Ferrostatin-1, which inhibits ferroptosis, resulted in increased Xcc growth. These data together highlight ferroptosis as a strategy against citrus canker in Ciron-05. CmOGD2 is positively regulated by the transcription factor CmZAT10, which binds upstream of the CmOGD2 start site. CmZAT10-dependent activation of CmOGD2 is required for elevated ROS and ferroptosis. To explain how this response is restrained, Hao et al. identified the enolase CmENO2 as a putative interacting partner of CmOGD2 by yeast 2-hybrid and in planta interactions studies. Inhibiting enolase activity with sodium fluoride reduced Xcc growth and disease symptoms consistent with CmENO2 acting as a negative regulator of resistance. Sodium fluoride treatment also decreased CmZAT10 levels, which would likely reduce CmOGD2 expression. The authors therefore propose that CmENO2 dampens ferroptosis in uninfected tissue by suppressing CmOGD2 via CmZAT10. During infection, the Xcc effector pthA4 may likely disrupt the CmOGD2–CmZAT10 interaction, relieving CmOGD2 of repression, increasing CmZAT10 levels, and thereby boosting CmOGD2 expression, iron uptake, and ferroptotic defense. These data support a regulatory mechanism of CmOGD2 under basal conditions and during Xcc infection (Figure). Thus, it turns out that too much of some things can, sometimes, be good. Here, Hao and colleagues highlight a case for excess iron in defense against citrus canker. Given the advances in single-cell transcriptomics, it would be intriguing to map cell type–specific iron and ROS dynamics during Xcc infection to pinpoint where CmOGD2-driven ferroptosis occurs, thereby providing deeper mechanistic insights to inform resistance breeding. The following phenotypic, genotypic, and functional terms are of significance to the work described in this paper: FSD1 Gramene: At4g25100 FSD1 Araport: At4g25100 sodium fluoride Gramene: EO:0007568 sodium fluoride Araport: EO:0007568