How tissue damage MET metabolism: Regulation of the systemic damage response

Abstract

Living organisms experience tissue damage from both, the surrounding environment and from inside their bodies. Tissue repair/regeneration is triggered by local tissue injury to restore an injured, or lost, part of the body. Tissue damage results in a series of responses, not only locally but also systemically in distant tissues. In our recent publication, we established a “dual system” that induces spatiotemporal tissue damage simultaneously with gene manipulation in surrounding tissues. With this system, we demonstrated that appropriate regulation of methionine metabolism in the fat body is required for tissue repair in Drosophila wing discs, thus highlighting the importance of systemic damage response (SDR) in tissue repair. This “Extra View” aims to discuss our recent reports that propose methionine metabolism to be an essential part of SDR, together with related topics in several model organisms.

Nutritional Control of Stem Cell Division through S-Adenosylmethionine in Drosophila Intestine

“…In this sense, it might be interesting to test whether metabolism in one tissue can systemically affect the stem cells in the other tissue. Our previous study demonstrating that fat body methionine metabolism can remotely influence the regenerative process in the imaginal wing discs supports this hypothesis (Kashio et al, 2016(Kashio et al, , 2017.…”

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

“…In addition to the Trp-Kyn pathway, another major metabolic pathway in the FB is the Met-SAM pathway ( Kashio et al., 2017 ). Our previous study indicated that the expression level of SAM synthase ( sams ) was upregulated in the FB of disc-cell-ablated larvae at AA6 and that sams in the FB was required for disc regeneration ( Kashio et al., 2016 ).…”

“…During blastema formation in a cut appendage, the contralateral uninjured appendage also shows cell proliferation via mTOR signaling ( Johnson et al., 2018 ). We are focusing on such systemic damage responses (SDRs), including systemic wound responses (SWRs) ( Kashio et al., 2017 ). When wounding by simple pricking was performed in adult Drosophila cuticle, an inter-tissue reaction was observed in the intestine and neurons, which are necessary for host survival ( Lee and Miura, 2014 ).…”

“…This could be greatly enhanced by tissue-specific and comprehensive genetic analyses. Previously, we established a genetic cell ablation system for studying non-autonomous aspects of tissue repair in Drosophila ( Kashio et al., 2016 , 2017 ). Drosophila larvae possesses regenerative tissues, imaginal discs, which are known to show a remarkable ability to repair massive tissue damage with surgical ablation or genetic temporal ablation ( Worley et al., 2012 ; Fox et al., 2020 ).…”

Involvement of neuronal tachykinin-like receptor at 86C in Drosophila disc repair via regulation of kynurenine metabolism

“…Tissue damage responses are not locally restricted; remote tissues also respond to local tissue damage, known as the systemic damage response or systemic wound response. 10 , 11 Recent studies have revealed the non-autonomous effects of remote tissues on regeneration. Our previous studies have indicated that imaginal disc repair is supported by the fat body in Drosophila larvae.…”