The role of cholesterol and mitochondrial bioenergetics in activation of the inflammasome in IBD
Inflammatory Bowel Disease (IBD) is characterized by a loss of intestinal barrier function caused by an aberrant interaction between the immune response and the gut microbiota. In IBD, imbalance in cholesterol homeostasis and mitochondrial bioenergetics have been identified as essential events for a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1028953/full |
| _version_ | 1797295089664393216 |
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| author | Jessica Astorga Naschla Gasaly Naschla Gasaly Naschla Gasaly Karen Dubois-Camacho Karen Dubois-Camacho Marjorie De la Fuente Glauben Landskron Klaas Nico Faber Félix A. Urra Marcela A. Hermoso Marcela A. Hermoso |
| author_facet | Jessica Astorga Naschla Gasaly Naschla Gasaly Naschla Gasaly Karen Dubois-Camacho Karen Dubois-Camacho Marjorie De la Fuente Glauben Landskron Klaas Nico Faber Félix A. Urra Marcela A. Hermoso Marcela A. Hermoso |
| author_sort | Jessica Astorga |
| collection | DOAJ |
| description | Inflammatory Bowel Disease (IBD) is characterized by a loss of intestinal barrier function caused by an aberrant interaction between the immune response and the gut microbiota. In IBD, imbalance in cholesterol homeostasis and mitochondrial bioenergetics have been identified as essential events for activating the inflammasome-mediated response. Mitochondrial alterations, such as reduced respiratory complex activities and reduced production of tricarboxylic acid (TCA) cycle intermediates (e.g., citric acid, fumarate, isocitric acid, malate, pyruvate, and succinate) have been described in in vitro and clinical studies. Under inflammatory conditions, mitochondrial architecture in intestinal epithelial cells is dysmorphic, with cristae destruction and high dynamin-related protein 1 (DRP1)-dependent fission. Likewise, these alterations in mitochondrial morphology and bioenergetics promote metabolic shifts towards glycolysis and down-regulation of antioxidant Nuclear erythroid 2-related factor 2 (Nrf2)/Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) signaling. Although the mechanisms underlying the mitochondrial dysfunction during mucosal inflammation are not fully understood at present, metabolic intermediates and cholesterol may act as signals activating the NLRP3 inflammasome in IBD. Notably, dietary phytochemicals exhibit protective effects against cholesterol imbalance and mitochondrial function alterations to maintain gastrointestinal mucosal renewal in vitro and in vivo conditions. Here, we discuss the role of cholesterol and mitochondrial metabolism in IBD, highlighting the therapeutic potential of dietary phytochemicals, restoring intestinal metabolism and function. |
| first_indexed | 2024-03-07T21:41:43Z |
| format | Article |
| id | doaj.art-8ac7b5a3542f4b9ab2c4452751ecb692 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-07T21:41:43Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8ac7b5a3542f4b9ab2c4452751ecb6922024-02-26T08:51:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10289531028953The role of cholesterol and mitochondrial bioenergetics in activation of the inflammasome in IBDJessica Astorga0Naschla Gasaly1Naschla Gasaly2Naschla Gasaly3Karen Dubois-Camacho4Karen Dubois-Camacho5Marjorie De la Fuente6Glauben Landskron7Klaas Nico Faber8Félix A. Urra9Marcela A. Hermoso10Marcela A. Hermoso11Laboratory of Innate Immunity, Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, ChileLaboratory of Innate Immunity, Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, ChileImmunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, NetherlandsDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, NetherlandsLaboratory of Innate Immunity, Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, ChileLaboratory of Metabolic Plasticity and Bioenergetics, Program of Molecular and Clinical Pharmacology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, ChileLaboratory of Biomedicine Research, School of Medicine, Universidad Finis Terrae, Santiago, ChileLaboratory of Biomedicine Research, School of Medicine, Universidad Finis Terrae, Santiago, ChileDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, NetherlandsLaboratory of Metabolic Plasticity and Bioenergetics, Program of Molecular and Clinical Pharmacology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, ChileLaboratory of Innate Immunity, Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, ChileDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, NetherlandsInflammatory Bowel Disease (IBD) is characterized by a loss of intestinal barrier function caused by an aberrant interaction between the immune response and the gut microbiota. In IBD, imbalance in cholesterol homeostasis and mitochondrial bioenergetics have been identified as essential events for activating the inflammasome-mediated response. Mitochondrial alterations, such as reduced respiratory complex activities and reduced production of tricarboxylic acid (TCA) cycle intermediates (e.g., citric acid, fumarate, isocitric acid, malate, pyruvate, and succinate) have been described in in vitro and clinical studies. Under inflammatory conditions, mitochondrial architecture in intestinal epithelial cells is dysmorphic, with cristae destruction and high dynamin-related protein 1 (DRP1)-dependent fission. Likewise, these alterations in mitochondrial morphology and bioenergetics promote metabolic shifts towards glycolysis and down-regulation of antioxidant Nuclear erythroid 2-related factor 2 (Nrf2)/Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) signaling. Although the mechanisms underlying the mitochondrial dysfunction during mucosal inflammation are not fully understood at present, metabolic intermediates and cholesterol may act as signals activating the NLRP3 inflammasome in IBD. Notably, dietary phytochemicals exhibit protective effects against cholesterol imbalance and mitochondrial function alterations to maintain gastrointestinal mucosal renewal in vitro and in vivo conditions. Here, we discuss the role of cholesterol and mitochondrial metabolism in IBD, highlighting the therapeutic potential of dietary phytochemicals, restoring intestinal metabolism and function.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1028953/fullIBD - inflammatory bowel diseaseintracellular cholesterol accumulationmitochondrial dysfunctioninflammasomeNLRP3 inflammasomediet phytochemicals |
| spellingShingle | Jessica Astorga Naschla Gasaly Naschla Gasaly Naschla Gasaly Karen Dubois-Camacho Karen Dubois-Camacho Marjorie De la Fuente Glauben Landskron Klaas Nico Faber Félix A. Urra Marcela A. Hermoso Marcela A. Hermoso The role of cholesterol and mitochondrial bioenergetics in activation of the inflammasome in IBD Frontiers in Immunology IBD - inflammatory bowel disease intracellular cholesterol accumulation mitochondrial dysfunction inflammasome NLRP3 inflammasome diet phytochemicals |
| title | The role of cholesterol and mitochondrial bioenergetics in activation of the inflammasome in IBD |
| title_full | The role of cholesterol and mitochondrial bioenergetics in activation of the inflammasome in IBD |
| title_fullStr | The role of cholesterol and mitochondrial bioenergetics in activation of the inflammasome in IBD |
| title_full_unstemmed | The role of cholesterol and mitochondrial bioenergetics in activation of the inflammasome in IBD |
| title_short | The role of cholesterol and mitochondrial bioenergetics in activation of the inflammasome in IBD |
| title_sort | role of cholesterol and mitochondrial bioenergetics in activation of the inflammasome in ibd |
| topic | IBD - inflammatory bowel disease intracellular cholesterol accumulation mitochondrial dysfunction inflammasome NLRP3 inflammasome diet phytochemicals |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1028953/full |
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