title: Apoptosis-Inducing-Factor-Dependent Mitochondrial Function Is Required for T Cell but Not B Cell Function.
abstract: The role of apoptosis inducing factor (AIF) in promoting cell death versus survival remains controversial. We report that the loss of AIF in fibroblasts led to mitochondrial electron transport chain defects and loss of proliferation that could be restored by ectopic expression of the yeast NADH dehydrogenase Ndi1. Aif-deficiency in T cells led to decreased peripheral T cell numbers and defective homeostatic proliferation, but thymic T cell development was unaffected. In contrast, Aif-deficient B cells developed and functioned normally. The difference in the dependency of T cells versus B cells on AIF for function and survival correlated with their metabolic requirements. Ectopic Ndi1 expression rescued homeostatic proliferation of Aif-deficient T cells. Despite its reported roles in cell death, fibroblasts, thymocytes and B cells lacking AIF underwent normal death. These studies suggest that the primary role of AIF relates to complex I function, with differential effects on T and B cells.
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Milasta
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Dillon
authors.affiliation: Department of Biology, Rhodes College, 2000 North Parkway, Memphis, TN 38112, USA.
authors.forename: Oliver E
authors.initials: OE
authors.lastname: Sturm
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Verbist
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Taylor L
authors.initials: TL
authors.lastname: Brewer
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Quarato
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Brown
authors.affiliation: Cell and Tissue Imaging Center, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Frase
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Janke
authors.affiliation: Department of Flow Cytometry, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: S Scott
authors.initials: SS
authors.lastname: Perry
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Thomas
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA. Electronic address: douglas.green@stjude.org.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Green
mesh_terms: D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism*; D019069:Cell Respiration / Q000502:physiology; D042967:Electron Transport Complex I / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D051033:Apoptosis Inducing Factor; C494830:AIFM1 protein, mouse; D042967:Electron Transport Complex I