Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 26, Issue 6, Pages 2215-2225Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.26.6.2215-2225.2006
Keywords
-
Categories
Funding
- NIAMS NIH HHS [R01 AR049217, AR048269, AR049217, R01 AR048269] Funding Source: Medline
Ask authors/readers for more resources
Receptor-interacting protein (RIP) has been implicated in the induction of death receptor-mediated, non-apoptotic cell death. However, the mechanisms remain to be elucidated. Here we show that tumor necrosis factor alpha induced RIP-dependent inhibition of adenine nucleotide translocase (ANT)-conducted transport of ADP into mitochondria, which resulted in reduced ATP and necrotic cell death. The inhibition of ADP/ATP exchange coincided with the loss of interaction between ANT and cyclophilin D and the inability of ANT to adopt the cytosolic conformational state, which prevented cytochrome c release. Neither overexpression of Bcl-x(L) nor inhibition of reactive oxygen species prevented necrosis. In contrast, the ectopic expression of ANT or cyclophilin D was effective at preventing cell death. These observations demonstrate a novel mechanism initiated through death receptor ligation and mediated by RIP that results in the suppression of ANT activity and necrosis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available