Moreno-Sanchez 2022 Abstract Bioblast

6.2. «10+5» Moreno-Sanchez Rafael, Robledo-Cadena DX, Pacheco-Velázquez SC, Rodríguez-Enríquez S (2022) Estimation of energy pathway fluxes in cancer cells- beyond the Warburg effect. Bioblast 2022: BEC Inaugural Conference. In: https://doi.org/10.26124/bec:2022-0001

Link: Bioblast 2022: BEC Inaugural Conference

Moreno-Sanchez Rafael, Robledo-Cadena Diana Xochiquetzal, Pacheco-Velazquez Silvia Cecilia, Rodriguez-Enriquez Sara (2022)

Event: Bioblast 2022

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 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.

• Keywords: Oxidative phosphorylation, oxygen uptake, glycolysis, cell ATP supply, cancer cell migration

• O2k-Network Lab: MX Mexiko City Moreno-Sanchez R

Affiliations

Moreno-Sánchez Rafael^1*, Robledo-Cadena Diana Xochiquetzal², Pacheco-Velázquez Silvia Cecilia², Rodríguez-Enríquez Sara^3*

1. Facultad de Estudios Superiores Iztacala, UNAM, Tlanepantla, Estado de Mexico, Mexico
2. Departamento de Bioquímica, Instituto Nacional de Cardiología, Ciudad de México 14080. Mexico
3. Laboratorio de Control Metabólico, Carrera de Medicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México; Los Reyes Ixtacala, Hab. Los Reyes Ixtacala Barrio de los Árboles/Barrio de los Héroes, Tlalnepantla 54090, Mexico

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Event: B2