PMID- 36906097 OWN - NLM STAT- MEDLINE DCOM- 20230404 LR - 20230425 IS - 1096-0384 (Electronic) IS - 0003-9861 (Linking) VI - 739 DP - 2023 May 1 TI - Estimation of energy pathway fluxes in cancer cells - Beyond the Warburg effect. PG - 109559 LID - S0003-9861(23)00058-9 [pii] LID - 10.1016/j.abb.2023.109559 [doi] AB - Glycolytic and respiratory fluxes were analyzed in cancer and non-cancer cells. The steady-state fluxes in energy metabolism were used to estimate the contributions of aerobic glycolytic and oxidative phosphorylation (OxPhos) pathways 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 basal or endogenous cellular O(2) consumption corrected for non-ATP synthesizing O(2) consumption, measured after inhibition by oligomycin (a specific, potent and permeable ATP synthase inhibitor), has been proposed as the appropriate way to estimate mitochondrial ATP synthesis-linked O(2) flux or net OxPhos flux in living cells. Detecting non-negligible oligomycin-sensitive O(2) 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 different types of cancer cells, it was found that OxPhos pathway was the main ATP provider over glycolysis. Hence, OxPhos pathway 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. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Moreno-Sanchez, Rafael AU - Moreno-Sanchez R AD - Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Carrera de Biologia, Laboratorio de Control Metabolico, Los Reyes Ixtacala, Hab. Los Reyes Ixtacala Barrio de los Arboles/Barrio de los Heroes, Tlalnepantla, 54090, Mexico. Electronic address: rafael.moreno@iztacala.unam.mx. FAU - Robledo-Cadena, Diana Xochiquetzal AU - Robledo-Cadena DX AD - Instituto Nacional de Cardiologia, Departamento de Bioquimica, Ciudad de Mexico, 14080, Mexico. FAU - Pacheco-Velazquez, Silvia Cecilia AU - Pacheco-Velazquez SC AD - Instituto Nacional de Cardiologia, Departamento de Bioquimica, Ciudad de Mexico, 14080, Mexico. FAU - Vargas Navarro, Jorge Luis AU - Vargas Navarro JL AD - Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Carrera de Biologia, Laboratorio de Control Metabolico, Los Reyes Ixtacala, Hab. Los Reyes Ixtacala Barrio de los Arboles/Barrio de los Heroes, Tlalnepantla, 54090, Mexico. FAU - Padilla-Flores, Joaquin Alberto AU - Padilla-Flores JA AD - Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Carrera de Biologia, Laboratorio de Control Metabolico, Los Reyes Ixtacala, Hab. Los Reyes Ixtacala Barrio de los Arboles/Barrio de los Heroes, Tlalnepantla, 54090, Mexico. FAU - Rodriguez-Enriquez, Sara AU - Rodriguez-Enriquez S AD - Instituto Nacional de Cardiologia, Departamento de Bioquimica, Ciudad de Mexico, 14080, Mexico; Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Carrera de Medicina, Laboratorio de Control Metabolico, Los Reyes Ixtacala, Hab. Los Reyes Ixtacala Barrio de los Arboles/Barrio de los Heroes, Tlalnepantla, 54090, Mexico. Electronic address: saren960104@hotmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230309 PL - United States TA - Arch Biochem Biophys JT - Archives of biochemistry and biophysics JID - 0372430 RN - 8L70Q75FXE (Adenosine Triphosphate) SB - IM MH - *Adenosine Triphosphate/metabolism MH - Energy Metabolism MH - Glycolysis/physiology MH - Oxidative Phosphorylation MH - Citric Acid Cycle MH - *Neoplasms OTO - NOTNLM OT - ATP supply In cancer cells OT - Glycolysis OT - Metastasis OT - Oxidative phosphorylation COIS- Declaration of competing interest The authors declare no conflicts of interest. EDAT- 2023/03/12 06:00 MHDA- 2023/04/04 06:42 CRDT- 2023/03/11 19:28 PHST- 2022/10/24 00:00 [received] PHST- 2023/02/15 00:00 [revised] PHST- 2023/03/04 00:00 [accepted] PHST- 2023/04/04 06:42 [medline] PHST- 2023/03/12 06:00 [pubmed] PHST- 2023/03/11 19:28 [entrez] AID - S0003-9861(23)00058-9 [pii] AID - 10.1016/j.abb.2023.109559 [doi] PST - ppublish SO - Arch Biochem Biophys. 2023 May 1;739:109559. doi: 10.1016/j.abb.2023.109559. Epub 2023 Mar 9.