Analysis of HIV Protease Killing Through Caspase 8 Reveals a Novel Interaction Between Caspase 8 and Mitochondria

Alicia Algeciras-Schimnich, Anne Sophie Belzacq-Casagrande, Gary D. Bren, Zilin Nie, Julie A. Taylor, Stacey Rizza, Catherine Brenner, Andrew David Badley

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)39-46
Number of pages8
JournalThe open virology journal
Volume1
DOIs
StatePublished - Dec 27 2007

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Caspase 8
Cytochromes c
Mitochondria
Peptide Hydrolases
Cell Death
HIV
Apoptosis
Caspase 9
Caspases
Cysteine
Peptides

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Analysis of HIV Protease Killing Through Caspase 8 Reveals a Novel Interaction Between Caspase 8 and Mitochondria. / Algeciras-Schimnich, Alicia; Belzacq-Casagrande, Anne Sophie; Bren, Gary D.; Nie, Zilin; Taylor, Julie A.; Rizza, Stacey; Brenner, Catherine; Badley, Andrew David.

In: The open virology journal, Vol. 1, 27.12.2007, p. 39-46.

Research output: Contribution to journalArticle

Algeciras-Schimnich, Alicia ; Belzacq-Casagrande, Anne Sophie ; Bren, Gary D. ; Nie, Zilin ; Taylor, Julie A. ; Rizza, Stacey ; Brenner, Catherine ; Badley, Andrew David. / Analysis of HIV Protease Killing Through Caspase 8 Reveals a Novel Interaction Between Caspase 8 and Mitochondria. In: The open virology journal. 2007 ; Vol. 1. pp. 39-46.
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