Analysis of HIV Protease Killing Through Caspase 8 Reveals a Novel Interaction Between Caspase 8 and Mitochondria
Alicia Algeciras-Schimnich1, Anne-Sophie Belzacq-Casagrande3, Gary D Bren1, Zilin Nie1, Julie A Taylor1, Stacey A Rizza1, Catherine Brenner3, Andrew D Badley*, 1, 2
Identifiers and Pagination:Year: 2007
First Page: 39
Last Page: 46
Publisher Id: TOVJ-1-39
Article History:Received Date: 7/11/2007
Revision Received Date: 19/11/2007
Acceptance Date: 3/12/2007
Electronic publication date: 27/12/2007
Collection year: 2007
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.
Human Immunodeficiency Virus (HIV) protease initiates apoptosis of HIV-infected cells by proteolytic cleavage of procaspase 8, creating a novel peptide termed casp8p41. Expression of casp8p41 alone is sufficient to initiate caspase-dependent cell death associated with mitochondrial depolarization. Since casp8p41 does not contain the catalytic cysteine at position 360, the mechanism by which casp8p41 initiates apoptosis is unclear. We demonstrate that casp8p41 directly causes mitochondrial depolarization and release of cytochrome c with downstream caspase 9 activation. Moreover, death induced by casp8p41 requires the presence of mitochondria, and in intact cells, casp8p41 colocalizes with mitochondria. These results illuminate a novel mechanism of cell death induced by a caspase 8 cleavage fragment whereby mitochondrial interaction leads to depolarization and cytochrome c release.