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How inorganic phosphate (Pi) homeostasis is regulated in  Drosophila  is currently unknown. We here identify  MFS 2 as a key Pi transporter in fly renal (Malpighian) tubules. Consistent with its role in Pi excretion, we found that dietary Pi induces  MFS2  expression. This results in the formation of Malpighian calcium-Pi stones, while RNAi-mediated knockdown of  MFS2  increases blood (hemolymph) Pi and decreases formation of Malpighian tubule stones in flies cultured on high Pi medium. Conversely, microinjection of adults with the phosphaturic human hormone  fibroblast growth factor 23  ( FGF23 ) induces tubule expression of  MFS2  and decreases blood Pi. This action of  FGF23  is blocked by genetic ablation of  MFS2 . Furthermore, genetic overexpression of the fly  FGF branchless (bnl)  in the tubules induces expression of  MFS2  and increases Malpighian tubule stones suggesting that  bnl  is the endogenous phosphaturic hormone in adult flies. Finally, genetic ablation of  MFS2  increased fly life span, suggesting that Malpighian tubule stones are a key element whereby high Pi diet reduces fly longevity previously reported by us. In conclusion,  MFS2  mediates excretion of Pi in  Drosophila , which is as in higher species under the hormonal control of  FGF-signaling .

Endocrine regulation of MFS2 by branchless controls phosphate excretion and stone formation in Drosophila renal tubules