Talk:Moreno-Sanchez 2022 Abstract Bioblast

Version 2

Glycolytic and mitochondrial ADP→ATP phosphorylation is tightly controlled in cancer and non-cancer cells. The steady-state fluxes in energy metabolism are used to estimate the glycolytic (anaerobic in the presence of oxygen) 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. Indeed, the glycolytic rates estimated for cancer cells were higher than those found in non-cancer cells, as originally observed by Otto Warburg. The rate of ROUTINE cellular O₂ consumption R corrected for LEAK respiration L measured after inhibition by oligomycin (a specific, potent and permeable ATP synthase inhibitor) is the respiratory R-L net ROUTINE capacity proposed as the appropriate way to estimate mitochondrial ADP-linked O₂ 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 the 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 inhibitors can be successfully used to block ATP-dependent processes such as cellular migration in cancer cells. These observations may guide the re-design of novel targeted therapies.

Version 1

The experimental determination of the glycolytic and oxidative phosphorylation (OXPHOS) fluxes in cancer and non-cancer cells is analyzed. The steady-state energy metabolism fluxes are in turn used to estimate their respective contributions to the cellular ATP supply. The rate of lactate production, corrected for the fraction generated by glutaminolysis, is proposed as the more appropriate way to estimate glycolysis flux. Indeed, the glycolysis rates estimated for cancer cells are higher than those found in non-cancer cells, as originally observed by Otto Warburg. The rate of total cellular O₂ consumption corrected by using oligomycin, a specific, potent and permeable ATP synthase inhibitor, is proposed as the more appropriate way to estimate OXPHOS flux. 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 the cellular ATP supply, under a variety of environmental conditions and for several different types of cancer cells, it is found that OXPHOS is the main ATP provider over glycolysis. Hence, it is shown that to block ATP-dependent processes such as cellular migration in cancer cells, OXPHOS inhibitors can be successfully used. These observations may guide the re-design of novel targeted therapies.