ArticleFree radical biology & medicine2022
Mitochondrial interaction of fibrosis-protective 5-methoxy tryptophan enhances collagen uptake by macrophages.
Article in Free radical biology & medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Tracing NADCell reports · 2026Article
- The effect of 5MTP on the expression of inflammatory markers in human aortic endothelial cell.Acta diabetologica · 2026Article
- Monovalent pseudo-natural products supercharge degradation of IDO1 by its native E3 KLHDC3.Nature chemistry · 2026Article
- Tracing NADResearch square · 2025Article
- Unraveling the proteomic landscape of fibrosis in lupus nephritis through CI-based analysis.Clinical rheumatology · 2024Article
- Predictive Value of 5-Methoxytryptophan on Long-Term Clinical Outcome after PCI in Patients with Acute Myocardial Infarction-a Prospective Cohort Study.Journal of cardiovascular translational research · 2024Article
- 5-Methoxytryptophan Alleviates Lipopolysaccharide-Induced Acute Kidney Injury by Regulating Nrf2-Mediated Mitophagy.Journal of inflammation research · 2024Article
- 5-Methoxytryptophan Alleviates Dextran Sulfate Sodium-Induced Colitis by Inhibiting the Intestinal Epithelial Damage and Inflammatory Response.Mediators of inflammation · 2024Article
- A quantitativeMethodsX · 2023Article
- Development of [Journal of medicinal chemistry · 2023Article
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
5-methoxy tryptophan (5-MTP) is an anti-fibrotic metabolite made by fibroblasts and epithelial cells, present in a micromolar concentrations in human blood, and is associated with the progression of fibrotic kidney disease, but the mechanism is unclear. Here, we show by microscopy and functional assays that 5-MTP influences mitochondria in human peripheral blood monocyte-derived macrophages. As a result, the mitochondrial membranes are more rigid, more branched, and are protected against oxidation. The macrophages also change their metabolism by reducing mitochondrial import of acyl-carnitines, intermediates of fatty acid metabolism, driving glucose import. Moreover, 5-MTP increases the endocytosis of collagen by macrophages, and experiments with inhibition of glucose uptake showed that this is a direct result of their altered metabolism. However, 5-MTP does not affect the macrophages following pathogenic stimulation, due to 5-MTP degradation by induced expression of indole-amine oxygenase-1 (IDO-1). Thus, 5-MTP is a fibrosis-protective metabolite that, in absence of pathogenic stimulation, promotes collagen uptake by anti-inflammatory macrophages by altering the physicochemical properties of their mitochondrial membranes.
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