ArticleNature metabolism2024
PNPO-PLP axis senses prolonged hypoxia in macrophages by regulating lysosomal activity.
Article in Nature metabolism, 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 16 papers.
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Who cites it
16 citing papers in PubMed.
- Hypoxia in MASLD: a spatial determinant of the pathogenesis.Trends in molecular medicine · 2026Review
- The iron-sulfur cluster assembly factor FDX2 is required for tumor initiation but not for growth of established tumors in transplantation models.The Journal of biological chemistry · 2026Article
- Ferroptosis-driven immune remodeling in heart failure: the central role of macrophage reprogramming and impaired efferocytosis.Journal of nanobiotechnology · 2026Review
- Repurposing Hetrombopag for Multiple Myeloma by Targeting PNPO: A Celastrol-Inspired Approach.Basic & clinical pharmacology & toxicology · 2026Article
- Multifaceted roles for persulfide species in redox chemical biology.Nature chemical biology · 2026Review
- Source-renewing ectopic ApoB-TRL lipolysis in non-resolving ARDS: a testable spatial hypothesis.Frontiers in immunology · 2026Article
- Integration of Multi-Omics Data Identifies the Role of the Selenium-Related Gene PNPO and Pre-exhausted CD127Cancer informatics · 2026Article
- Article
- Mitochondria regulate the cell fate decisions of megakaryocyte-erythroid progenitors.Stem cell reports · 2025Article
- Biological and clinical implications of a model of surveillance immunity.The Journal of clinical investigation · 2025Review
- Cross-talk between mitophagy pathways in pre-eclampsia and gestational diabetes mellitus: a systematic analysis of shared molecular mechanisms.European journal of medical research · 2025Article
- Oxygen needs sulfur, sulfur needs oxygen: a relationship of interdependence.The EMBO journal · 2025Review
- Article
- Microenvironments of tuberculous granuloma: advances and opportunities for therapy.Frontiers in immunology · 2025Review
- Acute hypoxia modulate macrophage phenotype accompanied with transcriptome re-programming and metabolic re-modeling.Frontiers in immunology · 2025Article
- Crosstalk between oxygen signaling and iron metabolism in renal interstitial fibroblasts.Journal of clinical biochemistry and nutrition · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
26 authors.
Funding
Abstract
Oxygen is critical for all metazoan organisms on the earth and impacts various biological processes in physiological and pathological conditions. While oxygen-sensing systems inducing acute hypoxic responses, including the hypoxia-inducible factor pathway, have been identified, those operating in prolonged hypoxia remain to be elucidated. Here we show that pyridoxine 5'-phosphate oxidase (PNPO), which catalyses bioactivation of vitamin B6, serves as an oxygen sensor and regulates lysosomal activity in macrophages. Decreased PNPO activity under prolonged hypoxia reduced an active form of vitamin B6, pyridoxal 5'-phosphate (PLP), and inhibited lysosomal acidification, which in macrophages led to iron dysregulation, TET2 protein loss and delayed resolution of the inflammatory response. Among PLP-dependent metabolism, supersulfide synthesis was suppressed in prolonged hypoxia, resulting in the lysosomal inhibition and consequent proinflammatory phenotypes of macrophages. The PNPO-PLP axis creates a distinct layer of oxygen sensing that gradually shuts down PLP-dependent metabolism in response to prolonged oxygen deprivation.
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