Scientific Publications by FDA Staff

J Cell Sci 2008 Jan 1;121(Pt 1):99-109

Conservation of the pro-apoptotic nuclease activity of endonuclease G in unicellular trypanosomatid parasites.

Gannavaram S, Vedvyas C, Debrabant A

Debrabant, A (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA

Endonuclease G is a mitochondrial protein implicated in DNA fragmentation during apoptosis in cell types ranging from fungi to mammals. Features of programmed cell death have been reported in a number of single-celled organisms, including the human trypanosomatid parasites Leishmania and Trypanosoma. However, the protozoan cell death pathways and the effector molecules involved in such processes remain to be identified. In this report, we describe the pro-apoptotic function of endonuclease G in trypanosomatid parasites. Similar to metazoans, trypanosome endoG showed intrinsic nuclease activity, is localized in mitochondria and is released from this organelle when cell death is triggered. Overexpression of endoG strongly promoted apoptotic cell death under oxidant or differentiation-related stress in Leishmania and, conversely, loss of endoG expression conferred robust resistance to oxidant-induced cell death in T. brucei. These data demonstrate the conservation of the pro-apoptotic endonuclease activity of endoG in these evolutionarily ancient eukaryotic organisms. Furthermore, nuclear DNA degradation by endoG upon release from mitochondria might represent a caspase-independent cell death mechanism in trypanosomatid parasites as genes encoding caspase-like proteins have not been identified in their genomes.