Molecular mechanisms governing Arabidopsis iron uptake

•Arabidopsis employs reduction-based Fe-deficiency-induced Fe uptake.•Multiple novel transcriptional regulators of Fe uptake have recently been identified.•IRT1 gene expression responds to developmental and environmental cues.•IRT1 localization and stability emerge as important factors in Fe-uptake regulation. Plants are the principal source of dietary iron (Fe) for most of Earth's population and Fe deficiency can lead to major health problems. Developing strategies to improve plant Fe content is a challenge because Fe is essential and toxic and therefore regulating Fe uptake is crucial for plant survival. Acquiring soil Fe relies on complex regulatory events that occur in root epidermal cells. We review recent advances in elucidating many aspects of the regulation of Fe acquisition. These include the expanding protein network involved in FER-LIKE IRON DEFICIENCY INDUCED TRANSCRIPTION FACTOR (FIT)-dependent gene regulation and novel findings on the intracellular trafficking of the Fe transporter IRON-REGULATED TRANSPORTER 1 (IRT1). We outline future challenges and propose strategies, such as exploiting natural variation, to further expand our knowledge.