Kynurenine Metabolism in the Fat Body Non-autonomously Regulates Imaginal Disc Repair in Drosophila

Soshiro Kashio; Masayuki Miura

doi:10.1016/j.isci.2020.101738

Kynurenine Metabolism in the Fat Body Non-autonomously Regulates Imaginal Disc Repair in Drosophila

iScience. 2020 Nov 6;23(12):101738. doi: 10.1016/j.isci.2020.101738. eCollection 2020 Dec 18.

Authors

Soshiro Kashio¹, Masayuki Miura¹

Affiliation

¹ Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Abstract

Tissue interactions are critical for maintaining homeostasis; however, little is known about how remote tissue regulates regeneration. Previously, we established a genetic dual system that induces cell ablation in Drosophila larval imaginal discs and simultaneously manipulates genes in non-damaged tissues. Using humoral metabolome analysis and a genetic damage system, we found that the Tryptophan (Trp)-Kynurenine (Kyn) pathway in the fat body is required for disc repair. Genetic manipulation of Trp-Kyn metabolism in the fat body impaired disc regeneration without affecting wing development. In particular, the fat body-derived humoral kynurenic acid (KynA) was required for disc repair. The impairment of S-adenosylmethionine (SAM) synthesis from methionine (Met) in the fat body hampers the maintenance of KynA levels in hemolymph at the early stage of disc repair, suggesting a connection between Met-SAM and Trp-Kyn metabolisms. Our data indicate KynA from the fat body acts as a permissive metabolite for tissue repair and regeneration.

Keywords: Biological Sciences; Cell Biology; Developmental Biology; Molecular Biology.