Iron is essential to cells as a cofactor in enzymes of respiration and replication, however without correct storage, iron leads to the formation of dangerous oxygen radicals. In yeast and plants, iron is transported into a membrane-bound vacuole by the vacuolar iron transporter (VIT). This transporter is conserved in the apicomplexan family of obligate intracellular parasites, including in Toxoplasma gondii. Here, we assess the role of VIT and iron storage in T. gondii. By deleting VIT, we find a slight growth defect in vitro, and iron hypersensitivity, confirming its essential role in parasite iron detoxification, which can be rescued by scavenging of oxygen radicals. We show VIT expression is regulated by iron at transcript and protein levels, and by altering VIT localization. In the absence of VIT, T. gondii responds by altering expression of iron metabolism genes and by increasing antioxidant protein catalase activity. We also show that iron detoxification has an important role both in parasite survival within macrophages and in virulence in a mouse model. Together, by demonstrating a critical role for VIT during iron detoxification in T. gondii, we reveal the importance of iron storage in the parasite and provide the first insight into the machinery involved.

铁作为呼吸和复制酶的辅助因子对细胞至关重要，但如果没有正确储存，铁会导致危险的氧自由基的形成。在酵母和植物中，铁通过液泡铁转运蛋白 (VIT) 转运到膜结合液泡中。这种转运蛋白在专性细胞内寄生虫的顶复门家族中是保守的，包括弓形虫。在这里，我们评估了 VIT 和铁储存在弓形虫中的作用。通过删除 VIT，我们在体外发现了轻微的生长缺陷和铁过敏，证实了其在寄生虫铁解毒中的重要作用，可以通过清除氧自由基来挽救。我们发现 VIT 表达在转录物和蛋白质水平上受到铁的调节，并通过改变 VIT 定位来调节。在缺乏 VIT 的情况下，弓形虫通过改变铁代谢基因的表达和增加抗氧化蛋白过氧化氢酶活性来做出反应。我们还表明，铁解毒对于巨噬细胞内寄生虫的存活和小鼠模型的毒力都具有重要作用。通过证明 VIT 在弓形虫铁解毒过程中的关键作用，我们共同揭示了铁储存在寄生虫中的重要性，并首次深入了解了所涉及的机制。