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.
| Original language | English |
|---|---|
| Pages (from-to) | 821-833 |
| Number of pages | 13 |
| Journal | Cell Reports |
| Volume | 7 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2014 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis. / Obata, Fumiaki; Kuranaga, Erina; Tomioka, Katsura; Ming, Ming; Takeishi, Asuka; Chen, Chun Hong; Soga, Tomoyoshi; Miura, Masayuki.
In: Cell Reports, Vol. 7, No. 3, 2014, p. 821-833.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis
AU - Obata, Fumiaki
AU - Kuranaga, Erina
AU - Tomioka, Katsura
AU - Ming, Ming
AU - Takeishi, Asuka
AU - Chen, Chun Hong
AU - Soga, Tomoyoshi
AU - Miura, Masayuki
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
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U2 - 10.1016/j.celrep.2014.03.046
DO - 10.1016/j.celrep.2014.03.046
M3 - Article
C2 - 24746817
AN - SCOPUS:84899935245
VL - 7
SP - 821
EP - 833
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 3
ER -