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 |
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Authors: | Manoj Kumar Tripathy Debashis Mitra |
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Institution: | (1) National Centre for Cell Science, Ganeshkhind, Pune, 411007, India; |
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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. |
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