|Moreno-Sánchez R, Robledo-Cadena DX, Pacheco-Velázquez SC, Rodríguez-Enríquez S (2022) Estimation of energy pathway fluxes in cancer cells- beyond the Warburg effect. https://doi.org/10.26124/mitofit:2022-0024|
» MitoFit Preprints 2022.24.
Abstract: Moreno-Sanchez 2022 Abstract Bioblast:Glycolytic and respiratory fluxes were analyzed in cancer and non-cancer cells. The steady-state fluxes in energy metabolism were used to estimate the aerobic glycolytic and mitochondrial (oxidative phosphorylation, OxPhos) contributions to the cellular ATP supply. The rate of lactate production ― corrected for the fraction generated by glutaminolysis ― is proposed as the appropriate way to estimate glycolytic flux. In general, the glycolytic rates estimated for cancer cells are higher than those found in non-cancer cells, as originally observed by Otto Warburg. The rate of ROUTINE R cellular O2 consumption corrected for LEAK respiration L measured after inhibition by oligomycin (a specific, potent and permeable ATP synthase inhibitor) becomes the respiratory R-L net ROUTINE capacity, which is proposed as the appropriate way to estimate mitochondrial ATP synthesis-linked O2 flux or net OxPhos flux in living cells. Detecting non-negligible O2 consumption rates in cancer cells has revealed that the mitochondrial function is not impaired, as claimed by the Warburg effect. Furthermore, when calculating the relative contributions to cellular ATP supply, under a variety of environmental conditions and for several different types of cancer cells, it was found that OxPhos was the main ATP provider over glycolysis. Hence, OxPhos targeting can be successfully used to block in cancer cells ATP-dependent processes such as migration. These observations may guide the re-design of novel targeted therapies. • Keywords: cell ATP supply; cancer cell migration; glycolysis; oxidative phosphorylation; oxygen uptake • Bioblast editor: Tindle-Solomon L • O2k-Network Lab: AT Innsbruck Oroboros, MX Mexiko City Moreno-Sanchez R
- Raw data used for this manuscript is available upon reasonable request to the corresponding author
- The present work was partially supported by CONACyT-México Grants No. 6379 to RMS; No. 377873 to SCPV and No. 283144 to SRE..