ArticleNature communications2024
PDCD6 regulates lactate metabolism to modulate LC3-associated phagocytosis and antibacterial defense.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Spatial and Temporal Heterogeneity of Macrophage Efferocytosis in Tumors: Emerging Implications for Immunotherapy Biomarkers and Therapeutic Timing.Cancer medicine · 2026Review
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- Systems-Level Multi-Omics Analysis Resolves the Mechanism of Action of a Novel Multifunctional Nanosystem Against Triple-Negative Breast Cancer.Pharmaceutics · 2026Article
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Glycolytic lactylation modulates cell death decisions in diabetic kidney disease: Metabolic‑epigenetic interplay between ferroptosis and autophagy in fibrotic remodeling (Review).International journal of molecular medicine · 2026Review
- Lactylation and acetylation: parallel paths, divergent deeds, and research dilemmas.Journal of translational medicine · 2026Review
- Article
- Integrated analysis of lactylation modification and proteomics revealed potential epigenetic regulation in intramuscular fat deposition of Xidu black pigs.BMC genomics · 2025Article
- Lysine lactylation in diseases: beyond histone lactylation.Cell death & disease · 2025Review
- ENKD1 attenuates antibacterial immunity by facilitating TRIM21-mediated RUBCN degradation to suppress LC3-associated phagocytosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Metabolic reprogramming of immune cells in the battle against intracellular bacterial chronic infections: novel mechanisms and breakthroughs.Molecular biology reports · 2025Review
- Hdac11 inhibits apoptosis in zebrafish cells under cold stress via downregulating pdcd6 through its downstream enhancer.Molecular biology reports · 2025Article
- Roles of lactylation in lipid metabolism and related diseases.Cell death discovery · 2025Review
- The role of bacterial metabolism in antimicrobial resistance.Nature reviews. Microbiology · 2025Review
- Lactylation-regulated biomolecular condensates: metabolic control of phase separation in physiology and disease.Cell communication and signaling : CCS · 2025Review
- Stereospecific lactylation in bacteriology: L/D-lactate partitioning shapes host metabolic-disease axis.Frontiers in microbiology · 2025Review
- Radiotherapy-induced alterations in tumor microenvironment: metabolism and immunity.Frontiers in cell and developmental biology · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
LC3-associated phagocytosis (LAP) is critical in host defense against invading pathogens, but the molecular mechanism for LAP activation is still unclear. Here, we find programmed cell death 6 (PDCD6) as a negative regulator of LAP. PDCD6 deficiency in mice and macrophages induces enhanced bactericidal activity and LAP formation. In parallel, lactate dehydrogenase A (LDHA) activity and lactate production is induced in macrophages challenged with bacteria, Zymosan or Pam3CSK4, while genetic ablation or pharmacological inhibition of LDHA reduces lactate levels and impairs bactericidal activity in vivo and in vitro. Mechanistically, PDCD6 interacts with LDHA to downregulate lactate metabolism, leading to reduced RUBCN lactylation at lysine33 (K33). By contrast, PDCD6-deficiency increases RUBCN lactylation, thereby promotes RUBCN interaction with VPS34, LAP formation, and protective responses. Our results thus suggest a PDCD6-LDHA-lactate-RUBCN axis of innate immunity regulation that may both contribute to protection from infectious diseases and serve as targets for therapeutic development.
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