Functional dissociation of Delta Psi m and cytochrome c release defines the contribution of mitochondria upstream of caspase activation during granzyme B-induced apoptosis

Waterhouse, N.J., Sedelies, K.A., Sutton, V.R., Pinkoski, M.J., Thia, K.Y., Johnstone, R., Bird, P.I., Green, D.R. and Trapani, J.A. (2006) Functional dissociation of Delta Psi m and cytochrome c release defines the contribution of mitochondria upstream of caspase activation during granzyme B-induced apoptosis. Cell Death and Differentiation, 13 4: 607-618. doi:10.1038/sj.cdd.4401772


Author Waterhouse, N.J.
Sedelies, K.A.
Sutton, V.R.
Pinkoski, M.J.
Thia, K.Y.
Johnstone, R.
Bird, P.I.
Green, D.R.
Trapani, J.A.
Title Functional dissociation of Delta Psi m and cytochrome c release defines the contribution of mitochondria upstream of caspase activation during granzyme B-induced apoptosis
Journal name Cell Death and Differentiation   Check publisher's open access policy
ISSN 1350-9047
1476-5403
Publication date 2006-04
Sub-type Article (original research)
DOI 10.1038/sj.cdd.4401772
Volume 13
Issue 4
Start page 607
End page 618
Total pages 12
Editor G. Melino
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Abstract Loss of Bid confers clonogenic survival to granzyme B-treated cells, however the exact role of Bid-induced mitochondrial damage - upstream or downstream of caspases - remains controversial. Here we show that direct cleavage of Bid by granzyme B, but not caspases, was required for granzyme B-induced apoptosis. Release of cytochrome c and SMAC, but not AIF or endonuclease G, occurred in the absence of caspase activity and correlated with the onset of apoptosis and loss of clonogenic potential. Loss of mitochondrial trans-membrane potential (Δψm) was also caspase independent, however if caspase activity was blocked the mitochondria regenerated their Δψm. Loss of Δψm was not required for rapid granzyme B-induced apoptosis and regeneration of Δψm following cytochrome c release did not confer clonogenic survival. This functional dissociation of cytochrome c and SMAC release from loss of Δψm demonstrates the essential contribution of Bid upstream of caspase activation during granzyme B-induced apoptosis.
Keyword Granzyme B
Cytochrome c
Apoptosis
Mitochondrial outer membrane permeabilization
Mitochondrial transmembrane potential
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Published online 16 September 2005.

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
School of Medicine Publications
 
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