IRON MAN (IMA) peptides, a family of small peptides, control iron (Fe) transport in plants, but their roles in Fe signaling remain unclear. BRUTUS (BTS) is a potential Fe sensor that negatively regulates Fe homeostasis by promoting the ubiquitin-mediated degradation of bHLH105 and bHLH115, two positive regulators of the Fe deficiency response. Here, we show that IMA peptides interact with BTS. The C-terminal parts of IMA peptides contain a conserved BTS interaction domain (BID) that is responsible for their interaction with the C terminus of BTS. Arabidopsis thaliana plants constitutively expressing IMA genes phenocopy the bts-2 mutant. Moreover, IMA peptides are ubiquitinated and degraded by BTS. bHLH105 and bHLH115 also share a BID, which accounts for their interaction with BTS. IMA peptides compete with bHLH105/bHLH115 for interaction with BTS, thereby inhibiting the degradation of these transcription factors by BTS. Genetic analyses suggest that bHLH105/bHLH115 and IMA3 have additive roles and function downstream of BTS. Moreover, the transcription of both BTS and IMA3 is activated directly by bHLH105 and bHLH115 under Fe-deficient conditions. Our findings provide a conceptual framework for understanding the regulation of Fe homeostasis: IMA peptides protect bHLH105/bHLH115 from degradation by sequestering BTS, thereby activating the Fe deficiency response.

IRON MAN (IMA) 肽是一个小肽家族，可控制植物中的铁 (Fe) 转运，但它们在 Fe 信号传导中的作用仍不清楚。BRUTUS (BTS) 是一种潜在的 Fe 传感器，它通过促进泛素介导的 bHLH105 和 bHLH115 的降解来负调节 Fe 稳态，bHLH105 和 bHLH115 是 Fe 缺乏反应的两个正调节剂。在这里，我们展示了 IMA 肽与 BTS 相互作用。IMA 肽的 C 末端部分包含一个保守的 BTS 相互作用域 (BID)，该结构域负责它们与 BTS 的 C 末端的相互作用。组成型表达IMA基因的拟南芥植物对bts-2进行表型复制突变体。此外，IMA 肽被 BTS 泛素化和降解。bHLH105 和 bHLH115 也共享一个 BID，这说明了它们与 BTS 的交互。IMA 肽与 bHLH105/bHLH115 竞争与 BTS 的相互作用，从而抑制 BTS 对这些转录因子的降解。遗传分析表明 bHLH105/bHLH115 和 IMA3 在 BTS 下游具有附加作用和功能。此外，在缺铁条件下，bHLH105 和 bHLH115 直接激活BTS和IMA3的转录。我们的研究结果为理解铁稳态的调节提供了一个概念框架：IMA 肽通过隔离 BTS 保护 bHLH105/bHLH115 免受降解，从而激活缺铁反应。