Journal Article Bcl-xL affects group a streptococcus-induced autophagy directly, by inhibiting fusion between autophagosomes and lysosomes, and indirectly, by inhibiting bacterial internalization via interaction with beclin 1-UVRAG

Nakajima, Shintaro  ,  Aikawa, Chihiro  ,  Nozawa, Takashi  ,  Minowa-Nozawa, Atsuko  ,  Toh, Hirotaka  ,  Nakagawa, Ichiro

12 ( 1 ) 2017-01-13 , Public Library of Science
ISSN:1932-6203
Description
Anti-apoptotic Bcl-2 and Bcl-xL are proposed to regulate starvation-induced autophagy by directly interacting with Beclin 1. Beclin 1 is also thought to be involved in multiple vesicle trafficking pathways such as endocytosis by binding to Atg14L and UVRAG. However, how the interaction of Bcl-2 family proteins and Beclin 1 regulates anti-bacterial autophagy (xenophagy) is still unclear. In this study, we analyzed these interactions using Group A Streptococcus (GAS; Streptococcus pyogenes) infection as a model. GAS is internalized into epithelial cells through endocytosis, while the intracellular fate of GAS is degradation by autophagy. Here, we found that Bcl-xL but not Bcl-2 regulates GAS-induced autophagy. Autophagosome-lysosome fusion and the internalization process during GAS infection were promoted in Bcl-xL knockout cells. In addition, knockout of Beclin 1 phenocopied the internalization defect of GAS. Furthermore, UVRAG interacts not only with Beclin 1 but also with Bcl-xL, and overexpression of UVRAG partially rescued the internalization defect of Beclin 1 knockout cells during GAS infection. Thus, our results indicate that Bcl-xL inhibits GASinduced autophagy directly by suppressing autophagosome-lysosome fusion and indirectly by suppressing GAS internalization via interaction with Beclin 1-UVRAG.
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http://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/218028/1/journal.pone.0170138.pdf

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