ArticleMucosal immunology2018
MDR1 deficiency impairs mitochondrial homeostasis and promotes intestinal inflammation.
Article in Mucosal immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Role of Mitochondria in Inflammatory Bowel Diseases: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- IL-10-STAT3 axis preserves epithelial mitochondrial homeostasis during bacterial challenge.Gut microbes · 2026Article
- Mapping mitochondria-associated research in inflammatory bowel disease: A bibliometric and network analysis.Medicine · 2026Article
- Effects of cuproptosis and its application in inflammatory bowel disease (Review).International journal of molecular medicine · 2026Review
- The importance of mitochondria and mitochondrial calcium signaling in health and disease: an updated outlook on inflammation.Journal of translational medicine · 2026Review
- Overexpression of mitochondrial STAT3 protein improves colonic inflammation and fibrosis in inflammatory bowel disease by enhancing mitochondrial function.Frontiers in immunology · 2026Article
- MDR1 promotes CD8 T cell persistence in tumors and protects against cytotoxic chemotherapy.bioRxiv : the preprint server for biology · 2025Article
- Article
- Gastrointestinal tract, its pathophysiology andWorld journal of gastroenterology · 2025Review
- Nutrient sensing in intestinal stem cell: Linking dietary nutrients to cellular metabolic regulation.World journal of stem cells · 2025Review
- Therapeutic mechanisms of exclusive enteral nutrition in Crohn's disease.Seminars in immunopathology · 2025Review
- CKMT1 deficiency contributes to mitochondrial dysfunction and promotes intestinal epithelial cell apoptosis via reverse electron transfer-derived ROS in colitis.Cell death & disease · 2025Article
- Unlocking Gut Health: The Potent Role of Stilbenoids in Intestinal Homeostasis.Animals : an open access journal from MDPI · 2025Review
- Protective role of ABCC drug subfamily resistance transporters (ABCC1-7) in intestinal inflammation.Immunologic research · 2025Article
- Identification and Experimental Validation of Oxidative Stress-Related Biomarkers in Ulcerative Colitis Using Machine Learning.Journal of inflammation research · 2025Article
- Myosin Vb Traffics P-Glycoprotein to the Apical Membrane of Intestinal Epithelial Cells.Gastroenterology · 2025Article
- Advance on establishment of pathological model of ulcerative colitis.Frontiers in veterinary science · 2025Review
- Unveiling the Cuproptosis in Colitis and Colitis-Related Carcinogenesis: A Multifaceted Player and Immune Moderator.Research (Washington, D.C.) · 2025Review
- Hexokinase 2 expression in apical enterocytes correlates with inflammation severity in patients with inflammatory bowel disease.BMC medicine · 2024Article
- Immunometabolism and mitochondria in inflammatory bowel disease: a role for therapeutic intervention?Disease models & mechanisms · 2024Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
The multidrug resistance-1 (MDR1) gene encodes an ATP-dependent efflux transporter that is highly expressed in the colon. In mice, loss of MDR1 function results in colitis with similarities to human inflammatory bowel diseases (IBD). Here, we show that MDR1 has an unexpected protective role for the mitochondria where MDR1 deficiency results in mitochondrial dysfunction with increased mitochondrial reactive oxygen species (mROS) driving the development of colitis. Exogenous induction of mROS accelerates, while inhibition attenuates colitis in vivo; these effects are amplified in MDR1 deficiency. In human IBD, MDR1 is negatively correlated to SOD2 gene expression required for mROS detoxification. To provide direct evidential support, we deleted intestinal SOD2 gene in mice and showed an increased susceptibility to colitis. We exploited the genome-wide association data sets and found many (∼5%) of IBD susceptibility genes with direct roles in regulating mitochondria homeostasis. As MDR1 primarily protects against xenotoxins via its efflux function, our findings implicate a distinct mitochondrial toxin+genetic susceptibility interaction leading to mitochondrial dysfunction, a novel pathogenic mechanism that could offer many new therapeutic opportunities for IBD.
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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.