Mitochondrial ATP Depletion Disrupts Caco-2 Monolayer Integrity and Internalizes Claudin 7

Frontiers in Physiology
Lonneke M JanssenDuijghuijsenJaap Keijer

Abstract

Objective:In vivo studies suggest that intestinal barrier integrity is dependent on mitochondrial ATP production. Here, we aim to provide mechanistic support, using an in vitro model mimicking the oxidative in vivo situation. Methods: Human Caco-2 cells were cultured for 10 days in culture flasks or for 14 days on transwell inserts in either glucose-containing or galactose-containing medium. Mitochondria were visualized and cellular respiration and levels of oxidative phosphorylation (OXPHOS) proteins were determined. Mitochondrial ATP depletion was induced using CCCP, rotenone, or piericidin A (PA). Monolayer permeability was assessed using transepithelial electrical resistance (TEER) and fluorescein flux. Gene expression and cellular distribution of tight junction proteins were analyzed. Results: Caco-2 cells cultured in galactose-containing, but not in glucose-containing, medium showed increased mitochondrial connectivity, oxygen consumption rates and levels of OXPHOS proteins. Inhibition of mitochondrial ATP production using CCCP, rotenone or PA resulted in a dose-dependent increase in Caco-2 monolayer permeability. In-depth studies with PA showed a six fold decrease in cellular ATP and revealed increased gene expression of...Continue Reading

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Citations

May 31, 2019·Frontiers in Veterinary Science·Mikayla F A BaxterGuillermo Tellez-Isaias
May 10, 2018·Veterinary Research·Richard DucatelleFilip Van Immerseel
Feb 5, 2021·Frontiers in Nutrition·Juan Carlos BórquezRoberto Bravo-Sagua
Jul 31, 2020·Current Opinion in Physiology·Susana Lechuga, Andrei I Ivanov
Jul 13, 2021·Frontiers in Cellular Neuroscience·Adonis SferaZisis Kozlakidis
Oct 2, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kana YokooTakuya Suzuki

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Methods Mentioned

BETA
protein assay
electrophoresis

Software Mentioned

NIH ImageJ
Graphpad Prism
Clarity Lite
CFX
Leica Application Suite X

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