Apoptosis Inducing Factor Binding Protein PGAM5 Triggers Mitophagic Cell Death That Is Inhibited by the Ubiquitin Ligase Activity of X-Linked Inhibitor of Apoptosis

Biochemistry ◽  
2016 ◽  
Vol 55 (23) ◽  
pp. 3285-3302 ◽  
Author(s):  
Audrey M. Lenhausen ◽  
Amanda S. Wilkinson ◽  
Eric M. Lewis ◽  
Kaitlin M. Dailey ◽  
Andrew J. Scott ◽  
...  
2007 ◽  
Vol 28 (1) ◽  
pp. 237-247 ◽  
Author(s):  
John C. Wilkinson ◽  
Amanda S. Wilkinson ◽  
Stefanie Galbán ◽  
Rebecca A. Csomos ◽  
Colin S. Duckett

ABSTRACT X-linked inhibitor of apoptosis (XIAP) is an inhibitor of apoptotic cell death that protects cells by caspase-dependent and independent mechanisms. In a screen for molecules that participate with XIAP in regulating cellular activities, we identified apoptosis-inducing factor (AIF) as an XIAP binding protein. Baculoviral IAP repeat 2 of XIAP is sufficient for the XIAP/AIF interaction, which is disrupted by Smac/DIABLO. In healthy cells, mature human AIF lacks only the first 54 amino acids, differing significantly from the apoptotic form, which lacks the first 102 amino-terminal residues. Fluorescence complementation and immunoprecipitation experiments revealed that XIAP interacts with both AIF forms. AIF was found to be a target of XIAP-mediated ubiquitination under both normal and apoptotic conditions, and an E3 ubiquitin ligase-deficient XIAP variant displayed a more robust interaction with AIF. Expression of either XIAP or AIF attenuated both basal and antimycin A-stimulated levels of reactive oxygen species (ROS), and when XIAP and AIF were expressed in combination, a cumulative decrease in ROS was observed. These results identify AIF as a new XIAP binding partner and indicate a role for XIAP in regulating cellular ROS.


2004 ◽  
Vol 16 (10) ◽  
pp. 2795-2808 ◽  
Author(s):  
Li-Rong Zeng ◽  
Shaohong Qu ◽  
Alicia Bordeos ◽  
Chengwei Yang ◽  
Marietta Baraoidan ◽  
...  

2004 ◽  
Vol 279 (26) ◽  
pp. 26906-26914 ◽  
Author(s):  
Emma M. Creagh ◽  
Brona M. Murphy ◽  
Patrick J. Duriez ◽  
Colin S. Duckett ◽  
Seamus J. Martin

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