PMID- 34073567
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210714
IS  - 2218-1989 (Print)
IS  - 2218-1989 (Electronic)
IS  - 2218-1989 (Linking)
VI  - 11
IP  - 6
DP  - 2021 May 26
TI  - Hyperosmolarity Triggers the Warburg Effect in Chinese Hamster Ovary Cells and 
      Reveals a Reduced Mitochondria Horsepower.
LID - 10.3390/metabo11060344 [doi]
LID - 344
AB  - 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 (DeltaPsim) but 
      mitochondrial horsepower seemed to vanish (h = Deltap/DeltaPsim), which may be explained by 
      mitochondrial hyperfusion.
FAU - da Veiga Moreira, Jorgelindo
AU  - da Veiga Moreira J
AUID- ORCID: 0000-0002-8020-9562
AD  - Research Laboratory in Applied Metabolic Engineering, Department of Chemical 
      Engineering, Ecole Polytechnique de Montreal, P.O. Box 6079, Centre-Ville 
      Station, Montreal, QC H3C 3A7, Canada.
FAU - De Staercke, Lenny
AU  - De Staercke L
AD  - Research Laboratory in Applied Metabolic Engineering, Department of Chemical 
      Engineering, Ecole Polytechnique de Montreal, P.O. Box 6079, Centre-Ville 
      Station, Montreal, QC H3C 3A7, Canada.
FAU - Cesar Martinez-Basilio, Pablo
AU  - Cesar Martinez-Basilio P
AD  - Research Laboratory in Applied Metabolic Engineering, Department of Chemical 
      Engineering, Ecole Polytechnique de Montreal, P.O. Box 6079, Centre-Ville 
      Station, Montreal, QC H3C 3A7, Canada.
FAU - Gauthier-Thibodeau, Sandrine
AU  - Gauthier-Thibodeau S
AD  - Research Laboratory in Applied Metabolic Engineering, Department of Chemical 
      Engineering, Ecole Polytechnique de Montreal, P.O. Box 6079, Centre-Ville 
      Station, Montreal, QC H3C 3A7, Canada.
FAU - Montegut, Lea
AU  - Montegut L
AD  - Research Laboratory in Applied Metabolic Engineering, Department of Chemical 
      Engineering, Ecole Polytechnique de Montreal, P.O. Box 6079, Centre-Ville 
      Station, Montreal, QC H3C 3A7, Canada.
FAU - Schwartz, Laurent
AU  - Schwartz L
AD  - Assistance Publique des Hopitaux de Paris, Avenue Victoria, 75003 Paris, France.
FAU - Jolicoeur, Mario
AU  - Jolicoeur M
AUID- ORCID: 0000-0002-0875-7265
AD  - Research Laboratory in Applied Metabolic Engineering, Department of Chemical 
      Engineering, Ecole Polytechnique de Montreal, P.O. Box 6079, Centre-Ville 
      Station, Montreal, QC H3C 3A7, Canada.
LA  - eng
PT  - Journal Article
DEP - 20210526
PL  - Switzerland
TA  - Metabolites
JT  - Metabolites
JID - 101578790
PMC - PMC8226498
OTO - NOTNLM
OT  - CHO cells
OT  - Warburg effect
OT  - hydroxycitrate
OT  - hyperosmolarity
OT  - lipoic acid
OT  - mitochondrial hyperfusion
COIS- The authors declare no conflict of interest.
EDAT- 2021/06/03 06:00
MHDA- 2021/06/03 06:01
PMCR- 2021/05/26
CRDT- 2021/06/02 01:38
PHST- 2021/04/23 00:00 [received]
PHST- 2021/05/18 00:00 [accepted]
PHST- 2021/06/02 01:38 [entrez]
PHST- 2021/06/03 06:00 [pubmed]
PHST- 2021/06/03 06:01 [medline]
PHST- 2021/05/26 00:00 [pmc-release]
AID - metabo11060344 [pii]
AID - metabolites-11-00344 [pii]
AID - 10.3390/metabo11060344 [doi]
PST - epublish
SO  - Metabolites. 2021 May 26;11(6):344. doi: 10.3390/metabo11060344.