Kinases Mst1 and Mst2 Positively Regulate Phagocytic Induction of Reactive Oxygen Species and Bactericidal Activity

Overview

Journal Nat Immunol

Date 2015 Sep 29

PMID 26414765

Citations 139

Authors

Jing Geng

Xiufeng Sun

Ping Wang

Shihao Zhang

Xiaozhen Wang

Hongtan Wu

Lixin Hong

Changchuan Xie

Xun Li

Hao Zhao

Qingxu Liu

Mingting Jiang

Qinghua Chen

Jinjia Zhang

Yang Li

Siyang Song

Hong-Rui Wang

Rongbin Zhou

Randy L Johnson

Kun-Yi Chien

Sheng-Cai Lin

Jiahuai Han

Joseph Avruch

Lanfen Chen

Dawang Zhou

Affiliations

Soon will be listed here.

Abstract

Mitochondria need to be juxtaposed to phagosomes for the synergistic production of ample reactive oxygen species (ROS) in phagocytes to kill pathogens. However, how phagosomes transmit signals to recruit mitochondria has remained unclear. Here we found that the kinases Mst1 and Mst2 functioned to control ROS production by regulating mitochondrial trafficking and mitochondrion-phagosome juxtaposition. Mst1 and Mst2 activated the GTPase Rac to promote Toll-like receptor (TLR)-triggered assembly of the TRAF6-ECSIT complex that is required for the recruitment of mitochondria to phagosomes. Inactive forms of Rac, including the human Rac2(D57N) mutant, disrupted the TRAF6-ECSIT complex by sequestering TRAF6 and substantially diminished ROS production and enhanced susceptibility to bacterial infection. Our findings demonstrate that the TLR-Mst1-Mst2-Rac signaling axis is critical for effective phagosome-mitochondrion function and bactericidal activity.

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