RESUMO
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.
Assuntos
Proteínas de Drosophila/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Glicina N-Metiltransferase/metabolismo , Sistema Imunitário/metabolismo , Necrose , S-Adenosilmetionina/metabolismo , Animais , Apoptose , Metilação de DNA , Drosophila/metabolismo , Proteínas de Drosophila/antagonistas & inibidores , Proteínas de Drosophila/genética , Metabolismo Energético , Metaboloma , Fenótipo , Sarcosina/metabolismo , Regulação para CimaRESUMO
Apoptosis is a fundamental way to remove damaged or unwanted cells during both developmental and post-developmental stages. Apoptosis deficiency leads to various diseases including cancer. To know the physiological changes in apoptosis-deficient mutants, we conducted non-biased transcriptomic analysis of Drosophila dark(cd4) mutants. As recently reported, combined with metabolome and genetic analysis, we identified systemic immune response, energy wasting, as well as alteration in S-adenosyl-methionine metabolism in response to necrotic cells [1]. Here, we describe in detail how we obtained validated microarray dataset deposited in Gene Expression Omnibus (GSE47853). Our data provide a resource for searching transcriptional alterations in Drosophila apoptosis-deficient mutants.