Fat body‐derived juvenile hormone acid methyltransferase functions to maintain iron homeostasis in Drosophila melanogaster

Abstract Iron homeostasis is of critical importance to living organisms. Drosophila melanogaster has emerged as an excellent model to study iron homeostasis, while the regulatory mechanism of iron metabolism remains poorly understood. Herein, we accidently found that knockdown of juvenile hormone (JH) acid methyltransferase ( Jhamt ) specifically in the fat body, a key rate‐limiting enzyme for JH synthesis, led to iron accumulation locally, resulting in serious loss and dysfunction of fat body. Jhamt knockdown‐induced phenotypes were mitigated by iron deprivation, antioxidant and Ferrostatin‐1, a well‐known inhibitor of ferroptosis, suggesting ferroptosis was involved in Jhamt knockdown‐induced defects in the fat body. Further study demonstrated that upregulation of Tsf1 and Malvolio ( Mvl , homolog of mammalian DMT1), two iron importers, accounted for Jhamt knockdown‐induced iron accumulation and dysfunction of the fat body. Mechanistically, Kr‐h1 , a key transcription factor of JH, acts downstream of Jhamt inhibiting Tsf1 and Mvl transcriptionally. In summary, the findings indicated that fat body‐derived Jhamt is required for the development of Drosophila by maintaining iron homeostasis in the fat body, providing unique insight into the regulatory mechanisms of iron metabolism in Drosophila .