Hyperosmolarity Triggers the Warburg Effect in Chinese Hamster Ovary Cells and Reveals a Reduced Mitochondria Horsepower

Hyperosmolarity Triggers the Warburg Effect in Chinese Hamster Ovary Cells and Reveals a Reduced Mitochondria Horsepower

Tumor cells are known to favor a glycolytic metabolism over oxidative phosphorylation (OxPhos), which takes place in mitochondria, to produce the energy and building blocks essential for cell maintenance and cell growth. This phenotypic property of tumor cells gives them several advantages over norm...

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Published in:Metabolites Vol. 11; no. 6; p. 344
Main Authors: da Veiga Moreira, Jorgelindo, De Staercke, Lenny, César Martínez-Basilio, Pablo, Gauthier-Thibodeau, Sandrine, Montégut, Léa, Schwartz, Laurent, Jolicoeur, Mario
Format: Journal Article
Language:English
Published: Basel MDPI AG 26-05-2021
MDPI
Subjects:
Acids
Bioenergetics
Calcium
Cancer therapies
Cell cycle
Cell division
Cell growth
Cell proliferation
CHO cells
Dehydrogenases
Drugs
Enzymes
Gene regulation
Genotype & phenotype
Glycolysis
hydroxycitrate
hyperosmolarity
Inflammation
Kinases
Lipoic acid
Mannitol
Membrane potential
Metabolic disorders
Metabolism
Mimicry
Mitochondria
mitochondrial hyperfusion
Osmolarity
Osmotic pressure
Ovaries
Oxidative metabolism
Oxidative phosphorylation
Phenotypes
Phosphorylation
Tumor cells
Tumors
Warburg effect
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Summary:Tumor cells are known to favor a glycolytic metabolism over oxidative phosphorylation (OxPhos), which takes place in mitochondria, to produce the energy and building blocks essential for cell maintenance and cell growth. This phenotypic property of tumor cells gives them several advantages over normal cells and is known as the Warburg effect. Tumors can be treated as a metabolic disease by targeting their bioenergetics capacity. Alpha-lipoic acid (ALA) and calcium hydroxycitrate (HCA) are two drugs known to target the Warburg effect in tumor cells and hence induce the mitochondria for ATP production. However, tumor cells, known to have an increased flux through glycolysis, are not able to handle the activation of their mitochondria by drugs or any other condition, leading to decoupling of gene regulation. In this study, these drug effects were studied by mimicking an inflammatory condition through the imposition of a hyperosmotic condition in Chinese hamster ovary (CHO) cells, which behave similarly to tumor cells. Indeed, CHO cells grown in high osmolarity conditions, using 200 mM mannitol, showed a pronounced Warburg effect phenotype. Our results show that hyperosmolar conditions triggered high-throughput glycolysis and enhanced glutaminolysis in CHO cells, such as during cancer cell proliferation in inflammatory tissue. Finally, we found that the hyperosmolar condition was correlated with increased mitochondrial membrane potential (ΔΨm) but mitochondrial horsepower seemed to vanish (h = Δp/ΔΨm), which may be explained by mitochondrial hyperfusion.
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ISSN:2218-1989
2218-1989
DOI:10.3390/metabo11060344