| 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
|
| Resource |
| Drosophila |
DGRC#119573
DGRC#119574
DGRC#119575
DGRC#119576
DGRC#119580 |
