Listeria monocytogenes upregulates mitochondrial calcium signalling to inhibit LC3-associated phagocytosis as a survival strategy
- 18 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Microbiology
- Vol. 6 (3), 366-379
- https://doi.org/10.1038/s41564-020-00843-2
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.Keywords
This publication has 84 references indexed in Scilit:
- Autophagosomes form at ER–mitochondria contact sitesNature, 2013
- Autophagy Protein Rubicon Mediates Phagocytic NADPH Oxidase Activation in Response to Microbial Infection or TLR StimulationCell Host & Microbe, 2012
- Listeriolysin O Suppresses Phospholipase C-Mediated Activation of the Microbicidal NADPH Oxidase to Promote Listeria monocytogenes InfectionCell Host & Microbe, 2011
- Autophagy machinery mediates macroendocytic processing and entotic cell death by targeting single membranesNature, 2011
- Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasomeNature Immunology, 2010
- Cellular Metabolic Stress: Considering How Cells Respond to Nutrient ExcessMolecular Cell, 2010
- Circulating mitochondrial DAMPs cause inflammatory responses to injuryNature, 2010
- Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilizationNature Immunology, 2008
- GROMACS: Fast, flexible, and freeJournal of Computational Chemistry, 2005
- AQUA and PROCHECK-NMR: Programs for checking the quality of protein structures solved by NMRJournal of Biomolecular NMR, 1996