Reference - Detail
| RRC ID | 83417 |
|---|---|
| Author | Obata F, Kuranaga E, Tomioka K, Ming M, Takeishi A, Chen CH, Soga T, Miura M. |
| Title | Necrosis-driven systemic immune response alters SAM metabolism through the FOXO-GNMT axis. |
| Journal | Cell Rep |
| Abstract |
Sterile inflammation triggered by endogenous factors is thought to contribute to the pathogenesis of acute and chronic inflammatory diseases. Here, we demonstrate that apoptosis-deficient mutants spontaneously develop a necrosis-driven systemic immune response in Drosophila and provide an in vivo model for studying the organismal response to sterile inflammation. Metabolomic analysis of hemolymph from apoptosis-deficient mutants revealed increased sarcosine and reduced S-adenosyl-methionine (SAM) levels due to glycine N-methyltransferase (Gnmt) upregulation. We showed that Gnmt was elevated in response to Toll activation induced by the local necrosis of wing epidermal cells. Necrosis-driven inflammatory conditions induced dFoxO hyperactivation, leading to an energy-wasting phenotype. Gnmt was cell-autonomously upregulated by dFoxO in the fat body as a possible rheostat for controlling energy loss, which functioned during fasting as well as inflammatory conditions. We propose that the dFoxO-Gnmt axis is essential for the maintenance of organismal SAM metabolism and energy homeostasis. |
| Volume | 7(3) |
| Pages | 821-33 |
| Published | 2014-5-8 |
| DOI | 10.1016/j.celrep.2014.03.046 |
| PII | S2211-1247(14)00243-5 |
| PMID | 24746817 |
| MeSH | Animals Apoptosis DNA Methylation Drosophila / metabolism Drosophila Proteins / antagonists & inhibitors Drosophila Proteins / genetics Drosophila Proteins / metabolism* Energy Metabolism Forkhead Transcription Factors / metabolism* Glycine N-Methyltransferase / metabolism* Immune System / metabolism* Metabolome Necrosis* Phenotype S-Adenosylmethionine / metabolism* Sarcosine / metabolism Up-Regulation |
| IF | 8.109 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 3 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Drosophila | DGRC#119573 DGRC#119574 DGRC#119575 DGRC#119576 DGRC#119580 |