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Immunity. 2016 Jan 19;44(1):88-102. doi: 10.1016/j.immuni.2015.12.002. Epub 2016 Jan 12.

Apoptosis-Inducing-Factor-Dependent Mitochondrial Function Is Required for T Cell but Not B Cell Function.

Author information

1
Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
2
Department of Biology, Rhodes College, 2000 North Parkway, Memphis, TN 38112, USA.
3
Department of Oncology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
4
Cell and Tissue Imaging Center, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
5
Department of Pathology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
6
Department of Flow Cytometry, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
7
Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA. Electronic address: douglas.green@stjude.org.

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.

Comment in

PMID:
26795252
PMCID:
PMC4936487
DOI:
10.1016/j.immuni.2015.12.002
[Indexed for MEDLINE]
Free PMC Article

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