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First published online 11 December 2007
doi: 10.1242/jcs.014050

Journal of Cell Science 121, 99-109 (2008)
Published by The Company of Biologists 2008
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Research Article

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

Sreenivas Gannavaram, Chetan Vedvyas and Alain Debrabant*

Laboratory of Bacterial, Parasitic and Unconventional Agents, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda MD 20892, USA

* Author for correspondence (e-mail: alain.debrabant{at}fda.hhs.gov)

Accepted 11 October 2007

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.

Key words: Trypanosomatid parasites, Programmed cell death, DNA fragmentation, Apoptotic Nucleases, Endonuclease G


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