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 language | English (US) |
|---|---|
| Pages (from-to) | 39-46 |
| Number of pages | 8 |
| Journal | The open virology journal |
| Volume | 1 |
| DOIs | |
| State | Published - Dec 27 2007 |
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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 journal › Article
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TY - JOUR
T1 - Analysis of HIV Protease Killing Through Caspase 8 Reveals a Novel Interaction Between Caspase 8 and Mitochondria
AU - Algeciras-Schimnich, Alicia
AU - Belzacq-Casagrande, Anne Sophie
AU - Bren, Gary D.
AU - Nie, Zilin
AU - Taylor, Julie A.
AU - Rizza, Stacey
AU - Brenner, Catherine
AU - Badley, Andrew David
PY - 2007/12/27
Y1 - 2007/12/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=62849087877&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=62849087877&partnerID=8YFLogxK
U2 - 10.2174/1874357900701010039
DO - 10.2174/1874357900701010039
M3 - Article
C2 - 18818773
VL - 1
SP - 39
EP - 46
JO - The open virology journal
JF - The open virology journal
SN - 1874-3579
ER -