Listeria monocytogenes upregulates mitochondrial calcium signalling to inhibit LC3-associated phagocytosis as a survival strategy

Tianliang Li, Ligang Kong, Xinghui Li, Sijin Wu, Kuldeep S. Attri, Yan Li, Weipeng Gong, Bao Zhao, Lupeng Li, Laura E. Herring, John M. Asara, Lei Xu, Xiaobo Luo, Yu L. Lei, Qin Ma, Stephanie Seveau, John S. Gunn, Xiaolin Cheng, Pankaj K. Singh, Douglas R. GreenHaibo Wang, Haitao Wen

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Mitochondria are believed to have originated ~2.5 billion years ago. As well as energy generation in cells, mitochondria have a role in defence against bacterial pathogens. Despite profound changes in mitochondrial morphology and functions following bacterial challenge, whether intracellular bacteria can hijack mitochondria to promote their survival remains elusive. We report that Listeria monocytogenes—an intracellular bacterial pathogen—suppresses LC3-associated phagocytosis (LAP) by modulation of mitochondrial Ca2+ (mtCa2+) signalling in order to survive inside cells. Invasion of macrophages by L. monocytogenes induced mtCa2+ uptake through the mtCa2+ uniporter (MCU), which in turn increased acetyl-coenzyme A (acetyl-CoA) production by pyruvate dehydrogenase. Acetylation of the LAP effector Rubicon with acetyl-CoA decreased LAP formation. Genetic ablation of MCU attenuated intracellular bacterial growth due to increased LAP formation. Our data show that modulation of mtCa2+ signalling can increase bacterial survival inside cells, and highlight the importance of mitochondrial metabolism in host–microbial interactions.

Original languageEnglish (US)
Pages (from-to)366-379
Number of pages14
JournalNature Microbiology
Volume6
Issue number3
DOIs
StatePublished - Mar 2021

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology

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