2. Academic Validation
  3. Listeria hijacks host mitophagy through a novel mitophagy receptor to evade killing

Listeria hijacks host mitophagy through a novel mitophagy receptor to evade killing

  • Nat Immunol. 2019 Apr;20(4):433-446. doi: 10.1038/s41590-019-0324-2.
Yifan Zhang 1,  Yikun Yao 1,  Xiaoxu Qiu 1,  Guodong Wang 1,  Zheng Hu 1,  Siyuan Chen 1,  Zhengxi Wu 1,  Na Yuan 2,  Hanchao Gao 1,  Jianrong Wang 2,  Houhui Song 3,  Stephen E Girardin 4,  Youcun Qian 5 6
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Tissue Microenvironment and Tumor, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
  • 2 Hematology Center of the Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology, State Key Laboratory of Radiation Medicine and Radioprotection, Soochow University School of Medicine, Suzhou, China.
  • 3 College of Animal Science and Technology, Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang A&F University, Lin'an, China.
  • 4 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, China.
  • 5 CAS Key Laboratory of Tissue Microenvironment and Tumor, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. ycqian@sibs.ac.cn.
  • 6 School of Life Science and Technology, ShanghaiTech University, Shanghai, China. ycqian@sibs.ac.cn.
PMID: 30804553 DOI: 10.1038/s41590-019-0324-2
Abstract

Cells use Mitophagy to remove damaged or unwanted mitochondria to maintain homeostasis. Here we report that the intracellular Bacterial pathogen Listeria monocytogenes exploits host Mitophagy to evade killing. We found that L. monocytogenes induced Mitophagy in macrophages through the virulence factor listeriolysin O (LLO). We discovered that NLRX1, the only NOD-like Receptor (NLR) family member with a mitochondrial targeting sequence, contains an LC3-interacting region (LIR) and directly associated with LC3 through the LIR. NLRX1 and its LIR motif were essential for L. monocytogenes-induced Mitophagy. NLRX1 deficiency and use of a Mitophagy inhibitor both increased mitochondrial production of Reactive Oxygen Species and thereby suppressed the survival of L. monocytogenes. Mechanistically, L. monocytogenes and LLO induced oligomerization of NLRX1 to promote binding of its LIR motif to LC3 for induction of Mitophagy. Our study identifies NLRX1 as a novel Mitophagy receptor and discovers a previously unappreciated strategy used by pathogens to hijack a host cell homeostasis system for their survival.

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