Table_1_MicroRNA-302/367 Cluster Impacts Host Antimicrobial Defense via Regulation of Mitophagic Response Against Pseudomonas aeruginosa Infection.doc (54.5 kB)
Download file

Table_1_MicroRNA-302/367 Cluster Impacts Host Antimicrobial Defense via Regulation of Mitophagic Response Against Pseudomonas aeruginosa Infection.doc

Download (54.5 kB)
dataset
posted on 07.10.2020, 10:24 by Ting Huang, Qinqin Pu, Chuanmin Zhou, Ping Lin, Pan Gao, Xiuyue Zhang, Yiwen Chu, Bisong Yue, Min Wu

Mitophagy has recently been implicated in bacterial infection but the underlying mechanism remains largely unknown. Here, we uncover a role of microRNA-302/367 cluster in regulating mitophagy and its associated host response against bacterial infection. We demonstrate that miR-302/367 cluster expression was significantly increased after Pseudomonas aeruginosa infection. Enhanced expression of miR-302/367 cluster accelerated the mitophagic response in macrophages, thus increasing clearance of invading P. aeruginosa by regulating production of reactive oxygen species (ROS), while application of miR-302/367 cluster inhibitors decreased bacterial clearance. Blocking mitophagy with siRNA against mitophagy receptor prohibitin 2 (PHB2) reduced the effect of miR-302/367 cluster on induction of mitophagy and its-associated P. aeruginosa elimination. In addition, we found that miR-302/367 cluster also increased bacterial clearance in mouse model. Mechanistically, we illustrate that miR-302/367 cluster binds to the 3′-untranslated region of nuclear factor kappa B (NF-κB), a negative regulator of mitophagy, accelerated the process of mitophagy by inhibiting NF-κB. Furthermore, inhibition of NF-κB in macrophages attenuated the ROS or cytokines production and may reduce cell injury by P. aeruginosa infection to maintain cellular homeostasis. Collectively, our findings elucidate that miR-302/367 cluster functions as potent regulators in mitophagy-mediated P. aeruginosa elimination and pinpoint an unexpected functional link between miRNAs and mitophagy.

History

References