Listeria monocytogenes upregulates mitochondrial calcium signaling to inhibit LC3-associated phagocytosis as a survival strategy
| Autor: | Xiaobo Luo, Haitao Wen, Lupeng Li, Xinghui Li, Bao Zhao, Stephanie Seveau, Qin Ma, Yan Li, John M. Asara, Tianliang Li, Sijin Wu, Weipeng Gong, Laura E. Herring, Douglas R. Green, John S. Gunn, Kuldeep S. Attri, Xiaolin Cheng, Lei Xu, Ligang Kong, Yu Lei, Haibo Wang, Pankaj K. Singh |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
Phagocytosis Immunology Autophagy-Related Proteins Mitochondrion medicine.disease_cause Applied Microbiology and Biotechnology Microbiology Article 03 medical and health sciences Mice Listeria monocytogenes Acetyl Coenzyme A Genetics medicine Animals Humans Calcium Signaling Uniporter 030304 developmental biology Calcium signaling 0303 health sciences 030306 microbiology Effector Chemistry Intracellular parasite Macrophages NADPH Oxidases Acetylation Cell Biology Cell biology Mitochondria Host-Pathogen Interactions Mutation Calcium Calcium Channels Microtubule-Associated Proteins Intracellular |
| Zdroj: | Nat Microbiol |
| Popis: | 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. Modulation of mitochondrial metabolism can increase the survival of intracellular bacteria such as Listeria monocytogenes inside cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|