Dynamin related protein 1‐dependent mitochondrial fission regulates oxidative signalling in T cells. Issue 9 (26th March 2014)

• Record Type: Journal Article
• Authors: Röth, Daniel; Krammer, Peter H.; Gülow, Karsten
• Is Part Of: FEBS letters. Volume 588:Issue 9(2014)
• Page Start: 1749
• Page End: 1754
• Publication Date: 2014-03-26
• Subjects: AICD -- activation induced cell death -- CFSE -- carboxyfluorescein succinimidyl ester -- DAG -- diacylglycerol -- Drp1 -- dynamin related protein 1 -- H2DCF-DA -- 2′, 7′-dichlorodihydrofluorescein diacetate -- IP3 -- inositol 3, 4, 5-triphosphate -- NAME -- NG-Nitroarginine methyl ester -- NMMA -- NG-monomethyl arginine -- PKC -- protein kinase C -- PMA -- phorbol 12-myristate 13-acetate -- ROS -- reactive oxygen species -- TCR -- T cell receptor -- T cell -- Interleukin -- Reactive oxygen species (ROS) -- Mitochondrial dynamics -- Dynamin related protein 1 (Drp1) -- Apoptosis -- Activation induced T cell death (AICD) -- CD95L/FASL; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2014.03.029
• Languages: English
• ISSNs: 0014-5793

Abstract

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. Abstract : Mitochondrial fission is required for activation‐induced ROS production in T cells. Drp1 activity is crucial for NF‐κB induced gene expression of IL‐2 and CD95L. Drp1 is activated by protein S‐nitrosylation.