Indan Journal of Medical Research Indan Journal of Medical Research Indan Journal of Medical Research
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REVIEW ARTICLE
Year : 2013  |  Volume : 138  |  Issue : 5  |  Page : 577-590

Role of apoptosis-inducing factor (Aif) in the T cell lineage


1 National Institute of Immunology, New Delhi, India
2 National Institute of Immunology, New Delhi, India; Laboratory of Molecular Biology & Immunology, National Institute of Aging, 251 Bayview Boulevard, Baltimore MD 21224, USA
3 National Institute of Immunology, New Delhi, India; Immune Disease Institute, Children's Hospital Boston, 3 Blackfan Circle, Boston MA 02115, USA
4 National Institute of Immunology, New Delhi, India; Division of Infectious Diseases, Department of Medicine, New York University School of Medicine, Smilow 901, 550 First Avenue, New York NY 10016, USA
5 National Institute of Immunology, New Delhi, India; MGH Cancer Center, Building 149, 13th Street, Charlestown, MA 02129, USA
6 National Institute of Immunology, New Delhi, India; Department of Surgery, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston SC 29425, USA
7 Department of Biological Sciences,University of Arkansas, Fayetteville, AR 72701, USA

Correspondence Address:
Satyajit Rath
National Institute of Immunology, Aruna Asaf Ali Road, New Delhi 110 067, India

Savit B Prabhu
National Institute of Immunology, Aruna Asaf Ali Road, New Delhi 110 067, India

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Source of Support: None, Conflict of Interest: None


PMID: 24434313

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Multiple checkpoints regulating finely balanced death-versus-survival decisions characterize both thymic development and peripheral homeostasis of T lymphocytes. While exploring the mechanisms of T cell death involved at various stages during the life of a T cell, we have observed and reported a variety of non-redundant roles for apoptosis inducing factor (Aif), a mitochondrial flavoprotein. Aif is ubiquitously expressed in all cell lineages and functions as an NADH oxidase in its mitochondrial location. It is released following the mitochondrial death signals, whereupon it translocates to the nucleus, binds to DNA and causes large-scale DNA fragmentation. During T cell development, Aif is important for developing thymocytes to navigate the double negative (DN)3 to DN4 transition (beta-selection), via its oxidoreductase property which protects the rapidly proliferating cells from death due to reactive oxygen species (ROS). In peripheral mature T cells, Aif deficiency leads to an increased susceptibility of T cell blasts to activation induced cell death (AICD), possibly mediated by its antioxidant function, and decreased sensitivity to neglect-induced death (NID). Thus, Aif seems to have pro-apoptotic and anti-apoptotic roles in the same lineage in different contexts and at different stages. Surprisingly, in the closely related B lymphocyte lineage, Aif deficiency does not result in any abnormality. These findings generate the possibility of specific T cell dysfunction in human disease caused by Aif deficiency, as well as in mitochondriopathies due to other causes. Also, these data raise questions regarding the basis of lineage-specific consequences of the dysfunction/deficiency of apparently ubiquitous molecules.


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