Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis
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 mo...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-05-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714002435 |
| _version_ | 1819018781992681472 |
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| author | Fumiaki Obata Erina Kuranaga Katsura Tomioka Ming Ming Asuka Takeishi Chun-Hong Chen Tomoyoshi Soga Masayuki Miura |
| author_facet | Fumiaki Obata Erina Kuranaga Katsura Tomioka Ming Ming Asuka Takeishi Chun-Hong Chen Tomoyoshi Soga Masayuki Miura |
| author_sort | Fumiaki Obata |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T03:24:53Z |
| format | Article |
| id | doaj.art-552bb35e2d024191a16dcee68b885a80 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T03:24:53Z |
| publishDate | 2014-05-01 |
| publisher | Elsevier |
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| series | Cell Reports |
| spelling | doaj.art-552bb35e2d024191a16dcee68b885a802022-12-21T19:17:37ZengElsevierCell Reports2211-12472014-05-017382183310.1016/j.celrep.2014.03.046Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT AxisFumiaki Obata0Erina Kuranaga1Katsura Tomioka2Ming Ming3Asuka Takeishi4Chun-Hong Chen5Tomoyoshi Soga6Masayuki Miura7Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, JapanLaboratory for Histogenetic Dynamics, RIKEN CDB, Kobe 650-0047, JapanDepartment of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, JapanNational Health Research Institutes, Zhunan, Miaoli County 35053, TaiwanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanDepartment of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, JapanSterile 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.http://www.sciencedirect.com/science/article/pii/S2211124714002435 |
| spellingShingle | Fumiaki Obata Erina Kuranaga Katsura Tomioka Ming Ming Asuka Takeishi Chun-Hong Chen Tomoyoshi Soga Masayuki Miura Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis Cell Reports |
| title | Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis |
| title_full | Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis |
| title_fullStr | Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis |
| title_full_unstemmed | Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis |
| title_short | Necrosis-Driven Systemic Immune Response Alters SAM Metabolism through the FOXO-GNMT Axis |
| title_sort | necrosis driven systemic immune response alters sam metabolism through the foxo gnmt axis |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714002435 |
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