ArticleNature microbiology2023
Parkinson's disease kinase LRRK2 coordinates a cell-intrinsic itaconate-dependent defence pathway against intracellular Salmonella.
Article in Nature microbiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- MARCH2/3 target FcγRI for K27-linked polyubiquitination and degradation to restrict the inflammatory response.Cellular & molecular immunology · 2026Article
- Itaconate metabolism in regulated cell death.Molecular and cellular biochemistry · 2026Review
- Offense and defense: itaconate mediates bidirectional immune regulation of host-bacteria interaction.Journal of biomedical science · 2026Review
- Quantitative three-dimensional imaging ofInfection and immunity · 2026Article
- How do immunometabolites shape bacterial infections?PLoS biology · 2026Article
- Itaconate transport across the plasma membrane and Salmonella-containing vacuole via MCT1/4 modulates macrophage antibacterial activity.Nature communications · 2025Article
- Salmonella multimutants enable efficient identification of SPI-2 effector protein function in gut inflammation and systemic colonization.Nature communications · 2025Article
- Intracellular Salmonella hijacks the mitochondrial citrate carrier to evade host oxidative defenses.Nature communications · 2025Article
- Proximity labelling reveals VPS13C as a regulator of Salmonella-containing vacuole fission.PLoS pathogens · 2025Article
- Modulation of host Rab GTPases by Salmonella: mechanisms of immune evasion and intracellular replication.Molecular biology reports · 2025Review
- The interplay betweenCell insight · 2025Review
- Salmonella exploits LRRK2-dependent plasma membrane dynamics to invade host cells.Nature communications · 2025Article
- Effect of pH and buffer on substrate binding and catalysis by cis-aconitate decarboxylase.Scientific reports · 2025Article
- Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A STING-CASM-GABARAP pathway activates LRRK2 at lysosomes.The Journal of cell biology · 2025Article
- Inducible antibacterial responses in macrophages.Nature reviews. Immunology · 2025Review
- Article
- The Evolution of Genetic Variability at theGenes · 2024Article
- RAB32 Ser71Arg in autosomal dominant Parkinson's disease: linkage, association, and functional analyses.The Lancet. Neurology · 2024Article
- Interferon-Science (New York, N.Y.) · 2024Review
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Cell-intrinsic defences constitute the first line of defence against intracellular pathogens. The guanosine triphosphatase RAB32 orchestrates one such defence response against the bacterial pathogen Salmonella, through delivery of antimicrobial itaconate. Here we show that the Parkinson's disease-associated leucine-rich repeat kinase 2 (LRRK2) orchestrates this defence response by scaffolding a complex between RAB32 and aconitate decarboxylase 1, which synthesizes itaconate from mitochondrial precursors. Itaconate delivery to Salmonella-containing vacuoles was impaired and Salmonella replication increased in LRRK2-deficient cells. Loss of LRRK2 also restored virulence of a Salmonella mutant defective in neutralizing this RAB32-dependent host defence pathway in mice. Cryo-electron tomography revealed tether formation between Salmonella-containing vacuoles and host mitochondria upon Salmonella infection, which was significantly impaired in LRRK2-deficient cells. This positions LRRK2 centrally within a host defence mechanism, which may have favoured selection of a common familial Parkinson's disease mutant allele in the human population.
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