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

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.

Role of mitochondrial pathway in compression-induced apoptosis of nucleus pulposus cells

“…In addition to the well-defined role of mitochondria in energy metabolism, regulation of cell apoptosis has recently emerged as second major function of these organelles [17][18][19][20][21][22]. Mitochondrion has an important role in caspase-dependant and caspase-independent pathways of apoptosis.…”

Mitochondrial Dihydrolipoamide Dehydrogenase Is Upregulated in Response to Intermittent Hypoxic Preconditioning

“…Measurement of mitochondrial complexes I, IV and V activities was also conducted as previously described using in-gel based assays 44. Activities for complexes II and III were measured spectrophotometrically as previously described 45, 46. Pyruvate dehydrogenase complex activity was determined according to the method of Schwab et al 47 and α-keto glutarate dehydrogenase complex activity was measured by the method described by Brown and Perham 48.…”

The cell death regulator GRIM-19 is involved in HIV-1 induced T-cell apoptosis

“…We used TNF-a and STS as inducers of apoptosis by intrinsic and extrinsic pathways respectively since we showed previously that these reagents induced apoptosis in CEM-GFP cells at the concentrations used [23]. It was observed that STS treated CEM-GFP cells had no significant change in GRIM-19 expression both at transcript and protein levels (Fig.…”

“…Induction of apoptosis in T cells by staurosporine (STS) and TNF-a A total of 5 9 10 6 CEM-GFP cells were either treated with 200 ng/ml TNF-a or with 1 lM of STS alongside untreated as control and incubated at 37°C in CO 2 incubator as described earlier [23]. Subsequently cells were either used for detecting apoptosis by flow cytometry or for RNA and/ or protein extraction.…”