On September, 28, 2015, Geng Jing and Sun Xiufeng, PhD
students of School of Life Sciences, Xiamen University published a cover paper
on Nature Immunology entitled “Kinases Mst1 and Mst2 positively regulate
phagocytic induction of reactive oxygen species and bactericidal activity”.
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 Rac2D57N 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.
The research is undertaken by Gen Jing of
PhD Class 2012, Sun Xiufeng of PhD Class 2013 and Wang Ping, Zhang Shihao and
Wang Xiaozhen, who are now in a research team led by Prof. Zhou Dawang and Chen
Lanfen, collaborating with Xiamen First Hopital, Changgeng University of Taiwan
andUniversityofScienceand Technology of
China. The research is funded by
"Thousand Youth Talents Plan", Chinese National Natural Science
Foundation and Ministry of Science and Technology.
Article Website:
http://www.nature.com/ni/journal/vaop/ncurrent/full/ni.3268.html