A Pathobiont Fragments Mitochondrial Networks in Epithelial Cells: Implications for Crohn’s Disease
| Autor: | Kim E. Barrett |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Mitochondrial Dynamics
Bacterial Adhesion EPEC enteropathogenic E coli GTPase guanosine triphosphatase Crohn Disease Medicine Intestinal Mucosa Original Research Crohn's disease Fis1 fission protein-1 IBD inflammatory bowel disease Drp1 dynamin-related peptide 1 PGC-1α peroxisome proliferator-activated receptor γ coactivator 1α Gastroenterology Mitochondria Editorial Caspase-3 Gene Knockdown Techniques Host-Pathogen Interactions AIF apoptosis inducing factor Epithelial Permeability Dynamins ATP adenosine triphosphate Colon MEDLINE Drp1 Permeability CCCP carbonyl cyanide m-chlorophenyl hydrazone ROS reactive oxygen species Text mining Cell Line Tumor Escherichia coli Humans TER transepithelial resistance Mitochondrial Fission and Fusion Bacteria OPA1 optic atrophy factor 1 Hepatology business.industry Gene Expression Profiling Human Epithelial Cell Lines Epithelial Cells medicine.disease CFU colony forming unit IL interleukin Gene Expression Regulation siRNA small interfering RNA Immunology business AIEC adherent invasive Escherichia coli |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology |
| ISSN: | 2352-345X |
| Popis: | Background & Aims Adherent-invasive Escherichia coli are implicated in inflammatory bowel disease, and mitochondrial dysfunction has been observed in biopsy specimens from patients with inflammatory bowel disease. As a novel aspect of adherent-invasive E coli–epithelial interaction, we hypothesized that E coli (strain LF82) would elicit substantial disruption of epithelial mitochondrial form and function. Methods Monolayers of human colon-derived epithelial cell lines were exposed to E coli–LF82 or commensal E coli and RNA sequence analysis, mitochondrial function (adenosine triphosphate synthesis) and dynamics (mitochondrial network imaging, immunoblotting for fission and fusion proteins), and epithelial permeability (transepithelial resistance, flux of fluorescein isothiocyanate–dextran and bacteria) were assessed. Results E coli–LF82 significantly affected epithelial expression of ∼8600 genes, many relating to mitochondrial function. E coli–LF82–infected epithelia showed swollen mitochondria, reduced mitochondrial membrane potential and adenosine triphosphate, and fragmentation of the mitochondrial network: events not observed with dead E coli–LF82, medium from bacterial cultures, or control E coli. Treatment with Mitochondrial Division Inhibitor 1 (Mdivi1, inhibits dynamin-related peptide 1, guanosine triphosphatase principally responsible for mitochondrial fission) or P110 (prevents dynamin-related peptide 1 binding to mitochondrial fission 1 protein) partially reduced E coli–LF82–induced mitochondrial fragmentation in the short term. E coli–LF82–infected epithelia showed loss of the long isoform of optic atrophy factor 1, which mediates mitochondrial fusion. Mitochondrial Division Inhibitor 1 reduced the magnitude of E coli–LF82–induced increased transepithelial flux of fluorescein isothiocyanate dextran. By 8 hours after infection, increased cytosolic cytochrome C and DNA fragmentation were apparent without evidence of caspase-3 or apoptosis inducing factor activation. Conclusions Epithelial mitochondrial fragmentation caused by E coli–LF82 could be targeted to maintain cellular homeostasis and mitigate infection-induced loss of epithelial barrier function. Data have been deposited in NCBI’s Gene Expression Omnibus and are accessible through GEO series accession numbers GSE154121 and GSE154122 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE154121). Graphical abstract |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|