Unknown

Dataset Information

0

Apoptosis-inducing factor (AIF) is targeted in IFN-?2a-induced Bid-mediated apoptosis through Bak activation in ovarian cancer cells.


ABSTRACT: Previously we have shown that interferon (IFN)-? induced apoptosis is predominantly mediated by the upregulation of tumor necrosis factor related apoptosis-inducing ligand (TRAIL) via the caspase-8 pathway. It was also shown that recruitment of mitochondria in IFN-? induced apoptosis involves the cleavage of BH3 interacting domain death agonist (Bid) to truncated Bid (tBid). In the present study, we demonstrate that tBid induced by IFN-?2a activates mitochondrial Bak to trigger the loss of mitochondrial membrane integrity, consequently causing release of apoptosis-inducing factor (AIF) in ovarian cancer cells, OVCAR3. AIF translocates from the mitochondria to the nucleus and induces nuclear fragmentation and cell death. Both a small molecule Bid inhibitor (BI-6C9) or Bid-RNA interference (RNAi) preserved mitochondrial membrane potential, prevented nuclear translocation of AIF, and abrogated IFN-?2a-induced cell death. Cell death induced by tBid was inhibited by AIF-RNAi, indicating that caspase-independent AIF signaling is the main pathway through which Bid mediates cell death. This was further supported by experiments showing that BI-6C9 did not prevent the release of cytochrome c from mitochondria to cytosol, while the release of AIF was prevented. In conclusion, IFN-?2a-induced apoptosis is mediated via the mitochondria-associated pathway involving the cleavage of Bid followed by AIF release that involves Bak activation and translocation of AIF from the mitochondria to the nucleus in OVCAR3 cells.

SUBMITTER: Miyake K 

PROVIDER: S-EPMC3389262 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

Apoptosis-inducing factor (AIF) is targeted in IFN-α2a-induced Bid-mediated apoptosis through Bak activation in ovarian cancer cells.

Miyake Kotaro K   Bekisz Joseph J   Zhao Tongmao T   Clark Christopher R CR   Zoon Kathryn C KC  

Biochimica et biophysica acta 20120607 8


Previously we have shown that interferon (IFN)-α induced apoptosis is predominantly mediated by the upregulation of tumor necrosis factor related apoptosis-inducing ligand (TRAIL) via the caspase-8 pathway. It was also shown that recruitment of mitochondria in IFN-α induced apoptosis involves the cleavage of BH3 interacting domain death agonist (Bid) to truncated Bid (tBid). In the present study, we demonstrate that tBid induced by IFN-α2a activates mitochondrial Bak to trigger the loss of mitoc  ...[more]

Similar Datasets

| S-EPMC4632302 | biostudies-literature
| S-EPMC3683554 | biostudies-literature
| S-EPMC3263500 | biostudies-literature
| S-EPMC5143395 | biostudies-literature
| S-EPMC3688461 | biostudies-literature
| S-EPMC5363526 | biostudies-literature
| S-EPMC7917670 | biostudies-literature
| S-EPMC2799216 | biostudies-literature
| S-EPMC7450093 | biostudies-literature
| S-EPMC5841295 | biostudies-literature