Dynamin related protein 1-dependent mitochondrial fission regulates oxidative signalling in T cells

AbstractIn 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