CITF1 fine-tunes FIT activity to regulate Fe uptake

Iron (Fe) is a vital micronutrient essential for plant growth and development. Under Fe-deficient conditions, plants activate their Fe uptake system to ensure adequate Fe supply. The FER-LIKE IRON DEFICIENCY INDUCED TRANSCRIPTION FACTOR (FIT) serves as a central regulator of the Fe uptake system, existing in both inactive and active states in Fe signaling regulation. Plants have evolved intricate mechanisms to modulate FIT activity in order to maintain Fe homeostasis. In this study, we uncover that the CU-DEFICIENCY INDUCED TRANSCRIPTION FACTOR 1 (CITF1) regulates Fe uptake by modulating FIT activity. Functional and genetic analyses demonstrate that CITF1 regulates Fe uptake in a FIT-dependent manner. Mechanistic investigations reveal that CITF1 modulates FIT activity through 3 distinct mechanisms: (i) interfering with BTSL1/2 interacting with FIT; (ii) hijacking FIT protein from the nucleus to the cytoplasm; and (iii) maintaining FIT in the FIT-CITF1 dimer to prevent FIT from activating Fe uptake genes. Collectively, our findings suggest that CITF1 regulates Fe uptake by fine-tuning FIT activity, thereby providing novel insights into the regulatory mechanisms of FIT.