Intracellular quercetin accumulation and its impact on mitochondrial dysfunction in intestinal Caco-2 cells

Hanne Vissenaekens; Guy Smagghe; Hanne Criel; Charlotte Grootaert; Katleen Raes; Andreja Rajkovic; Geert Goeminne; Nico Boon; Kristof De Schutter; John Van Camp

doi:10.1016/j.foodres.2021.110430

Intracellular quercetin accumulation and its impact on mitochondrial dysfunction in intestinal Caco-2 cells

Food Res Int. 2021 Jul:145:110430. doi: 10.1016/j.foodres.2021.110430. Epub 2021 May 20.

Authors

Affiliations

¹ Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Ghent 9000, Belgium; Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, Ghent 9000, Belgium.
² Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, Ghent 9000, Belgium.
³ Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Ghent 9000, Belgium.
⁴ VIB Metabolomics Core Ghent, VIB, Ghent 9052, Belgium; Department of Plant Biotechnology and Bioinformatics, Faculty of Sciences, Ghent University, Ghent 9052, Belgium.
⁵ Center for Microbial Ecology and Technology (CMET), Faculty of Bioscience Engineering, Ghent University, Ghent 9000, Belgium.
⁶ Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Ghent 9000, Belgium. Electronic address: john.vancamp@ugent.be.

PMID: 34112387
DOI: 10.1016/j.foodres.2021.110430

Abstract

Purpose: Flavonoid bioavailability and bioactivity is associated with interindividual variability, which is partially due to differences in health status. Previously, it was demonstrated that cellular stress, especially mitochondrial stress, increases intracellular quercetin uptake and this is associated with beneficial health effects. Here, the impact of quercetin on mitochondrial dysfunction, induced by stressors targeting different sites of the electron transport chain, is investigated. The influence of the mitochondrial stress on quercetin uptake and subcellular location is studied and the accumulated quercetin metabolites in intestinal Caco-2 cells and mitochondria are characterized.

Principal results: It was observed that quercetin counteracted (i) the carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP)-induced decrease in maximum oxygen consumption, (ii) the valinomycin-, oligomycin- and FCCP-induced reactive oxygen species production and (iii) the valinomycin-induced disruption of mitochondrial membrane potential. Using confocal microscopy, it was found that upon mitochondrial stress, the intracellular quercetin accumulation increased and was partially located in the mitochondria. Finally, it was demonstrated that quercetin was present as O-methyl, O-methylglucuronide and O-methylsulfate conjugates in the cell lysate and mitochondria-enriched fraction.

Major conclusions: This study shows that quercetin can partially restore, especially FCCP-induced, mitochondrial dysfunction and this protective effect was linked with an intracellular quercetin accumulation in the mitochondria of intestinal cells.

Keywords: Caco-2 cells; Flavonoid metabolism; Flavonoid uptake; Mitochondrial dysfunction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Caco-2 Cells
Humans
Membrane Potential, Mitochondrial
Mitochondria* / metabolism
Quercetin* / metabolism
Reactive Oxygen Species / metabolism

Substances

Reactive Oxygen Species
Quercetin