Apoptosis

, Volume 15, Issue 1, pp 28–40

Differential modulation of mitochondrial OXPHOS system during HIV-1 induced T-cell apoptosis: up regulation of Complex-IV subunit COX-II and its possible implications

Original Paper

DOI: 10.1007/s10495-009-0408-9

Cite this article as:
Tripathy, M.K. & Mitra, D. Apoptosis (2010) 15: 28. doi:10.1007/s10495-009-0408-9

Abstract

Human Immunodeficiency Virus-1 (HIV-1) infection leads to CD4+ T cell depletion primarily by apoptosis employing both intrinsic and extrinsic pathways. Although extensive literature exists about the role of mitochondrial proteins in HIV induced T cell apoptosis, there is little understanding about the role of different components of mitochondrial oxidative phosphorylation (OXPHOS) system in apoptosis. The OXPHOS system comprises of five enzyme complexes (Complex I, II, III, IV, V), subunits of which have been implicated in various functions in addition to their primary role in energy generating process. Here using differential gene expression analysis, we report that Cytochrome Oxidase-II (COX-II), a subunit of Complex-IV is induced in HIV infected apoptotic T-cells. We also observe a temporal up regulation of this subunit across different T-cell lines and in human PBMCs. Further analysis indicates increase in expression of majority of Complex-IV subunits with concomitant increase in Complex-IV activity in HIV infected T cells. Silencing of COX-II expression leads to reduced apoptosis in infected T-cells, indicating its importance in apoptosis. Furthermore, our results also show that the activities of enzyme complexes I, II and III are decreased while those of Complex IV and V are increased at the time of acute infection and apoptosis. This differential regulation in activities of OXPHOS system complexes indicate a complex modulation of host cell energy generating system during HIV infection that ultimately leads to T cell apoptosis.

Keywords

COX-IIBN-PAGEHIV-1ApoptosisOxidative phosphorylationComplex-IV

Abbreviations

OXPHOS

Oxidative phosphorylation

BN-PAGE

Blue native page

ADP

Adenosine 5′-diphosphate

ATP

Adenosine 5′-triphosphate

AZT

Azidothymidine

MOI

Multiplicity of infection

MTT

3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide

PBMC

Peripheral blood mononuclear cells

ROS

Reactive oxygen species

MOMP

Mitochondrial outer membrane potential

CcO

Cytochrome c Oxidase

Supplementary material

10495_2009_408_MOESM1_ESM.pdf (433 kb)
Supplementary material 1 (PDF 432 kb)

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.National Centre for Cell SciencePuneIndia