期刊
AUTOPHAGY
卷 18, 期 6, 页码 1401-1415出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2021.1987671
关键词
Macrophage; mitophagy; Mycobacterium bovis; p-TBK1; xenophagy
类别
资金
- National Natural Science Foundation of China [32172800, 31873005]
- High-end Foreign Experts Recruitment Program [GDW20151100036, GDW20161100071]
- MoSTRCUK international cooperation project [2013DFG32500]
- China Agriculture Research System [CARS-36]
- National Key Research and Development Program [2017YFD0500901]
Mitophagy, a selective autophagy mechanism for eliminating damaged mitochondria, plays a crucial role in immune evasion. Mycobacterium bovis utilizes host mitophagy to suppress xenophagy, enhancing its intracellular survival. The PINK1-PRKN/Parkin pathway is involved in M. bovis-induced mitophagy, with inhibition of mitophagy restricting bacterial survival in macrophages and mouse lungs. Induction of mitophagy competes with host xenophagy, highlighting a new insight into the intracellular survival mechanism of M. bovis.
Mitophagy is a selective autophagy mechanism for eliminating damaged mitochondria and plays a crucial role in the immune evasion of some viruses and bacteria. Here, we report that Mycobacterium bovis (M. bovis) utilizes host mitophagy to suppress host xenophagy to enhance its intracellular survival. M. bovis is the causative agent of animal tuberculosis and human tuberculosis. In the current study, we show that M. bovis induces mitophagy in macrophages, and the induction of mitophagy is impaired by PINK1 knockdown, indicating the PINK1-PRKN/Parkin pathway is involved in the mitophagy induced by M. bovis. Moreover, the survival of M. bovis in macrophages and the lung bacterial burden of mice are restricted by the inhibition of mitophagy and are enhanced by the induction of mitophagy. Confocal microscopy analysis reveals that induction of mitophagy suppresses host xenophagy by competitive utilization of p-TBK1. Overall, our results suggest that induction of mitophagy enhances M. bovis growth while inhibition of mitophagy improves growth restriction. The findings provide a new insight for understanding the intracellular survival mechanism of M. bovis in the host.
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