ArticleThe Journal of clinical investigation2015
NOTCH reprograms mitochondrial metabolism for proinflammatory macrophage activation.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
148 citing papers in PubMed, 243 citations in OpenAlex.
- Development and preclinical evaluation of a decoy DLL4-encoding oncolytic HSV-1 for high-grade glioma.Oncogene · 2026Article
- ATF7 drives diabetic wound healing via NOTCH1 repression and N1ICD-dependent macrophage polarization control.JCI insight · 2026Article
- Review
- Notch Signaling in Spinal Cord Injury: Mechanistic Insights and Therapeutic Perspectives.Molecular neurobiology · 2026Review
- Monocyte Dll4 Contributes to Systemic Inflammation in People Living With HIV.Circulation research · 2026Article
- Meta-inflammation through the lens of macrophage programming and nutrient-sensing ghrelin signaling.Immunometabolism (Cobham, Surrey) · 2026Review
- Exclusion of Notch from the contact site during efferocytosis restricts anticancer immunity.Nature immunology · 2026Article
- Homeostatic preservation of action potential waveform by Notch and Nerfin-1.Current biology : CB · 2026Article
- Role of myeloid cell transcription factor EB in alcohol-induced liver injury in mice.Liver research (Beijing, China) · 2026Article
- Oxidative Stress-Induced DNA Damage Response Pathways in Aortic Disease: Implications for Inflammation and Vascular Degeneration.International journal of molecular sciences · 2026Review
- Macrophage polarization in ischemia-reperfusion injury: from molecular mechanisms to therapeutic strategies.Frontiers in immunology · 2026Review
- What role does the Notch signaling pathway play in exercise-related metabolic and neurological adaptations? A molecular-to-systems perspective.Frontiers in physiology · 2026Review
- Interplay of human macrophage response and natural resistance of infection by L. (V.) panamensis to pentavalent antimony.PLoS neglected tropical diseases · 2025Article
- SIRT4 Regulated by a Mechanosensor, PIEZO1 Shows a Protective Function to Suppress Ox-LDL Uptake in Endothelial Cells.Tissue engineering and regenerative medicine · 2025Article
- The causal relationship between 91 inflammatory cytokines and chronic pancreatitis, and the mediating role of 1400 metabolites.Medicine · 2025Article
- NOTCH Signaling Networks in Perivascular Adipose Tissue.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Endometrial Aging and Reproductive Decline: The Central Role of Mitochondrial Dysfunction.International journal of molecular sciences · 2025Review
- Article
- Multifaceted Role of Notch Signaling in Vascular Health and Diseases.Biomedicines · 2025Review
- The Role of Notch Signaling and Gut Microbiota in Autoinflammatory Diseases: Mechanisms and Future Views.Biomedicines · 2025Review
88 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Metabolic reprogramming is implicated in macrophage activation, but the underlying mechanisms are poorly understood. Here, we demonstrate that the NOTCH1 pathway dictates activation of M1 phenotypes in isolated mouse hepatic macrophages (HMacs) and in a murine macrophage cell line by coupling transcriptional upregulation of M1 genes with metabolic upregulation of mitochondrial oxidative phosphorylation and ROS (mtROS) to augment induction of M1 genes. Enhanced mitochondrial glucose oxidation was achieved by increased recruitment of the NOTCH1 intracellular domain (NICD1) to nuclear and mitochondrial genes that encode respiratory chain components and by NOTCH-dependent induction of pyruvate dehydrogenase phosphatase 1 (Pdp1) expression, pyruvate dehydrogenase activity, and glucose flux to the TCA cycle. As such, inhibition of the NOTCH pathway or Pdp1 knockdown abrogated glucose oxidation, mtROS, and M1 gene expression. Conditional NOTCH1 deficiency in the myeloid lineage attenuated HMac M1 activation and inflammation in a murine model of alcoholic steatohepatitis and markedly reduced lethality following endotoxin-mediated fulminant hepatitis in mice. In vivo monocyte tracking further demonstrated the requirement of NOTCH1 for the migration of blood monocytes into the liver and subsequent M1 differentiation. Together, these results reveal that NOTCH1 promotes reprogramming of mitochondrial metabolism for M1 macrophage activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.