CG14075/Mmt promotes amino acid catabolism and cooperates with AKH during starvation in Drosophila

Abstract Starvation triggers the sequential mobilization of glycogen, lipids, and amino acids to sustain survival, yet the hormonal mechanisms coordinating these transitions remain poorly understood. Here, we identify CG14075/Marmite (Mmt) as a hormone-like peptide secreted from the corpora cardiaca (CC) of Drosophila melanogaster during prolonged nutrient deprivation. CG14075/Mmt is progressively released into the haemolymph during starvation, coinciding with the decline of glycogen and lipid stores. CG14075/Mmt contributes to the regulation of amino acid catabolism, with prominent effects on threonine and branched-chain amino acid metabolism, and its absence leads to amino acid accumulation associated with oxidative stress. Moreover, CG14075/Mmt functions alongside adipokinetic hormone (AKH), the lipid-catabolic glucagon-like hormone, to regulate lipid and amino acid metabolism during starvation. Loss of CG14075/Mmt accelerates lipid and glycogen consumption and reduces starvation resistance, phenotypes that are partly associated with increased AKH secretion. These findings reveal a CC-derived endocrine component that contributes to the coordinated utilization of multiple energy substrates during nutrient stress.