title: Dynamin related protein 1-dependent mitochondrial fission regulates oxidative signalling in T cells.
abstract: In T cells mitochondria-derived reactive oxygen species (ROS) are indispensible for activation of the transcription factor NF-κB, expression of cytokines and the CD95 ligand (CD95L/FasL). Here we show that activation-induced ROS generation is dependent on mitochondrial fission. Inhibition of dynamin related protein 1 (Drp1) results in reduced ROS levels and transcriptional activity of NF-κB leading to diminished proliferation and CD95L-dependent activation-induced cell death (AICD). Upon stimulation Drp1 is S-nitrosylated, which is required for oxidative signalling, AICD and cytokine production. In conclusion, we describe a novel signalling pathway that links TCR-induced nitric oxide release to mitochondrial fission and oxidative signalling.
authors.affiliation: Division of Immunogenetics (D030), Tumor Immunology Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Röth
authors.affiliation: Division of Immunogenetics (D030), Tumor Immunology Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Krammer
authors.affiliation: Division of Immunogenetics (D030), Tumor Immunology Program, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: k.guelow@dkfz.de.
authors.forename: Karsten
authors.initials: K
authors.lastname: Gülow
mesh_terms: D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D019169:Jurkat Cells; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D011499:Protein Processing, Post-Translational; D017382:Reactive Oxygen Species / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D026403:S-Nitrosothiols / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology*
chemical_list: D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D011948:Receptors, Antigen, T-Cell; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins
keywords: Activation induced T cell death (AICD); Apoptosis; CD95L/FASL; Dynamin related protein 1 (Drp1); Interleukin; Mitochondrial dynamics; Reactive oxygen species (ROS); T cell