Indan Journal of Medical Research Indan Journal of Medical Research Indan Journal of Medical Research
  Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login  
  Home Print this page Email this page Small font sizeDefault font sizeIncrease font size Users Online: 405       
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

Login to access the Email id

Source of Support: None, Conflict of Interest: None

PMID: 24434313

Rights and PermissionsRights and Permissions

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.

Print this article     Email this article
 Next article
 Previous article
 Table of Contents

 Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
 Citation Manager
 Access Statistics
 Reader Comments
 Email Alert *
 Add to My List *
 * Requires registration (Free)

 Article Access Statistics
    PDF Downloaded522    
    Comments [Add]    

Recommend this journal