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.
摘要：
铁稳态对活生物体至关重要。果蝇已经成为研究铁稳态的优秀模型，而铁代谢的调节机制仍然知之甚少。在这里，我们偶然发现，特别是脂肪体内的少年激素（JH）酸甲基转移酶（Jhamt）的敲除，JH合成的关键限速酶，导致当地的铁积累，导致身体脂肪严重流失和功能障碍。Jhamt敲除诱导的表型通过铁剥夺得到缓解，抗氧化剂和Ferrostatin-1，一种众所周知的铁凋亡抑制剂，提示铁性凋亡与Jhamt敲除诱导的脂肪体缺陷有关。进一步的研究表明，Tsf1和Malvolio(Mvl，哺乳动物DMT1的同源物)，两个铁进口商,解释了Jhamt敲除诱导的铁积累和脂肪体功能障碍。机械上,Kr-h1是JH的关键转录因子,在Jhamt的下游转录抑制Tsf1和Mvl。总之,研究结果表明，源自脂肪体的Jhamt通过维持脂肪体内的铁稳态来促进果蝇的发育，提供对果蝇铁代谢调节机制的独特见解。
