Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis

Fumiaki Obata, Erina Kuranaga, Katsura Tomioka, Ming Ming, Asuka Takeishi, Chun Hong Chen, Tomoyoshi Soga, Masayuki Miura

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 languageEnglish
Pages (from-to)821-833
Number of pages13
JournalCell Reports
Volume7
Issue number3
DOIs
Publication statusPublished - 2014

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Glycine N-Methyltransferase
Metabolism
Methionine
Necrosis
Sarcosine
Apoptosis
Inflammation
Fat Body
Metabolomics
Hemolymph
Energy Metabolism
Drosophila
Fasting
Energy dissipation
Homeostasis
Chronic Disease
Up-Regulation
Chemical activation
Fats
Maintenance

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Obata, F., Kuranaga, E., Tomioka, K., Ming, M., Takeishi, A., Chen, C. H., ... Miura, M. (2014). Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis. Cell Reports, 7(3), 821-833. https://doi.org/10.1016/j.celrep.2014.03.046

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 journalArticle

Obata, F, Kuranaga, E, Tomioka, K, Ming, M, Takeishi, A, Chen, CH, Soga, T & Miura, M 2014, 'Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis', Cell Reports, vol. 7, no. 3, pp. 821-833. https://doi.org/10.1016/j.celrep.2014.03.046
Obata, Fumiaki ; Kuranaga, Erina ; Tomioka, Katsura ; Ming, Ming ; Takeishi, Asuka ; Chen, Chun Hong ; Soga, Tomoyoshi ; Miura, Masayuki. / Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis. In: Cell Reports. 2014 ; Vol. 7, No. 3. pp. 821-833.
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