¹National Centre for Cell Science, Ganeshkhind, Pune 411007, India

Correspondence: D Mitra, National Centre for Cell Science, Pune University Campus, Ganeshkhind, Pune 411007, India. Tel: +91-20-25690931; Fax: +91-20-25692259; E-mail: dmitra@nccs.res.in, dmitra01@yahoo.co.in

Received 20 September 2004; Revised 11 April 2005; Accepted 12 April 2005; Published online 20 May 2005.

Abstract

Studies carried out till date to elucidate the pathways involved in HIV-1-induced T-cell depletion has revealed that apoptosis underlie the etiology, however, a clear molecular understanding of HIV-1-induced apoptosis has remained elusive. Although evidences pointing towards the importance of mitochondrial energy generating system in apoptosis exist but it's exact role remains to be clearly understood. Here, we describe for the first time specific downregulation of a complex I subunit NDUFA6 with simultaneous impairment of mitochondrial complex I activity in HIV infection. We also show that NDUFA6 gene silencing induces apoptosis and its overexpression reduces apoptosis in HIV-infected cells. Finally, sensitivity to complex I inhibitor Rotenone is reduced in HIV-1-infected T cells indicating an important role for it in the death process. Our data provide a novel molecular basis as to how the virus might interfere with host cell energy generating system during apoptotic cell death.