title: Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling.
abstract: It is widely appreciated that T cells increase glycolytic flux during activation, but the role of mitochondrial flux is unclear. Here, we have shown that mitochondrial metabolism in the absence of glucose metabolism is sufficient to support interleukin-2 (IL-2) induction. Furthermore, we used mice with reduced mitochondrial reactive oxygen species (mROS) production in T cells (T-Uqcrfs(-/-) mice) to show that mitochondria are required for T cell activation to produce mROS for activation of nuclear factor of activated T cells (NFAT) and subsequent IL-2 induction. These mice could not induce antigen-specific expansion of T cells in vivo, but Uqcrfs1(-/-) T cells retained the ability to proliferate in vivo under lymphopenic conditions. This suggests that Uqcrfs1(-/-) T cells were not lacking bioenergetically but rather lacked specific ROS-dependent signaling events needed for antigen-specific expansion. Thus, mitochondrial metabolism is a critical component of T cell activation through the production of complex III ROS.
authors: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors: Laura A
authors: LA
authors: Sena
authors: Sha
authors: S
authors: Li
authors: Amit
authors: A
authors: Jairaman
authors: Murali
authors: M
authors: Prakriya
authors: Teresa
authors: T
authors: Ezponda
authors: David A
authors: DA
authors: Hildeman
authors: Chyung-Ru
authors: CR
authors: Wang
authors: Paul T
authors: PT
authors: Schumacker
authors: Jonathan D
authors: JD
authors: Licht
authors: Harris
authors: H
authors: Perlman
authors: Paul J
authors: PJ
authors: Bryce
authors: Navdeep S
authors: NS
authors: Chandel
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D014450:Electron Transport Complex III / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D007506:Iron-Sulfur Proteins / Q000172:deficiency / Q000235:genetics; D008213:Lymphocyte Activation; D008231:Lymphopenia / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000235:genetics* / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics* / Q000276:immunology
chemical_list: D018398:Homeodomain Proteins; D007376:Interleukin-2; D007506:Iron-Sulfur Proteins; D050778:NFATC Transcription Factors; D017382:Reactive Oxygen Species; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C064658:RAG-1 protein; D014450:Electron Transport Complex III