RT Journal Article
SR Electronic
T1 The anti-apoptosis ubiquitin E3 ligase XIAP promotes autophagosome-lysosome fusion during autophagy
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 291294
DO 10.1101/291294
A1 Isabella Poetsch
A1 Petra Ebner
A1 Luiza Deszcz
A1 Iris Bachtrog
A1 Madlen Stephani
A1 Carlos Gómez Díaz
A1 Yasin Dagdas
A1 Fumiyo Ikeda
YR 2018
UL http://biorxiv.org/content/early/2018/03/29/291294.abstract
AB The Inhibitor of Apoptosis Protein (IAP) family members are well-known endogenous regulators of apoptosis. Whether these proteins regulate other degradation pathways is unclear. Here, we discovered that the IAP member X-linked IAP (XIAP) is crucial for macroautophagy. Loss of XIAP in mouse and human cells inhibited starvation-induced degradation of LC3 proteins and an autophagy substrate p62. It also led to the accumulation of mature autophagosomes, suggesting that XIAP controls autophagic flux by mediating autolysosome formation. Xiap∆RING/∆RING cells phenocopy the autophagy defects of Xiap−/− cells, suggesting that the ubiquitinating activity mediated by the catalytic RING domain is critical for autophagic flux. We found that XIAP physically interacts with Syntaxin 17, a regulator of autophagosome-lysosome fusion. Syntaxin 17-positive mature autophagosomes positive accumulate in the cytoplasm of starved Xiap−/− cells, suggesting that XIAP might regulate its dissociation from autophagosomes after fusion. XIAP selectively interacts with GABARAP among LC3 family members via the LIR-Docking Site (LDS). Together, our data suggest that XIAP-mediated ubiquitination regulates key autophagy regulators to promote autophagosome-lysosome fusion.