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

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. We thank Carlos Ribeiro and Patrícia Francisco for helpful discussions; Masayuki Miura, Michael B. O’Connor, the Drosophila Genomics Resource Center, the Bloomington Stock Center, the NIG-FLY Stock Center, and the Vienna Drosophila Resource Center for providing stocks and reagents; FlyBase for providing Drosophila genetic information; and SaKan Yoo for fruitful discussions and critical comments on the manuscript.

This study was conducted using research equipment provided by the Biosignal Genome Resource Center at Gunma University. This work was supported by JSPS KAKENHI Grant Number 23K14227 and AMED under Grant Number JP256f0137008 (to Y.Y.). This work was also partly supported by AMED-CREST (20gm1110001 to R.N.); the Cooperative Research Project Program of Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA Center), University of Tsukuba; the joint research program of the Institute for Molecular and Cellular Regulation, Gunma University (to R.N. and T.N.); the Mitsubishi Foundation in Natural Science (to Y.Y.); and the Takeda Science Foundation (to Y.Y.).

Present address: Department of Entomology, Institute for Integrative Genome Biology, University of California, Riverside, CA, USA Metabolic Regulation and Genetics, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Japan Yuto Yoshinari, Ryo Hoshino & Ryusuke Niwa Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan Maiko Abe, Ryo Hoshino, Yosuke Mizuno, Yoshitomo Kurogi & Eisuke Imura Department of Germline Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan Institute of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan Correspondence to Yuto Yoshinari, Ryusuke Niwa or Takashi Nishimura. The authors declare no competing interests. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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