Mitochondrial oxidative phosphorylation became functional under aglycemic hypoxia conditions in A549 cells


MOLECULAR BIOLOGY REPORTS, vol.49, no.9, pp.8219-8228, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 49 Issue: 9
  • Publication Date: 2022
  • Doi Number: 10.1007/s11033-022-07400-6
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.8219-8228
  • Keywords: A549 cells, Glucose metabolism, Oxidative phosphorylation, Tumor hypoxia, Warburg effect, PAS DOMAIN PROTEIN-1, INDUCIBLE FACTOR-I, PYRUVATE-DEHYDROGENASE KINASE, FACTOR 1-ALPHA, CANCER, EXPRESSION, METABOLISM, HIF-2-ALPHA, GENE, RESPIRATION
  • Anadolu University Affiliated: Yes


Background Normal cells produce energy (ATP) through mitochondrial oxidative phosphorylation in the presence of oxygen. However, many of the cancer cells produce energy with accelerated glycolysis and perform lactic acid production even under normoxic conditions called "The Warburg Effect". In this study, human lung carcinoma cells (A549) were incubated in either a normoxic or hypoxic environment containing 5 mM glucose (Glc 5), 25 mM glucose (Glc 25), or 10 mM galactose (OXPHOS/aglycemic), and then the bioenergetic pathway was anaylsed. Methods and results HIF-1 alpha stabilization of A549 cells with different metabolic conditions in normoxia and hypoxia (1% O-2) was determined using the western blot method. After that, l-lactic acid analysis, p-PDH/PDH expression ratio, ATP analysis, and citrate synthase activity experiments were also performed. It was determined that HIF-1 alpha stabilization reached the maximum level at the 4 h. It has been found that glycolytic cells produce approximately five times more lactate than OXPHOS cells under both normoxia and hypoxia conditions and also have a higher p-PDH/PDH ratio. It has been determined that citrate synthase activity in hypoxia of all metabolic conditions is lower than normoxia. It has been determined that Glc 5 and Glc 25 cells have more ATP production under normoxia than Glc 5 and Glc 25 cells in hypoxia. OXPHOS cells have showed more ATP production in hypoxia. Conclusion It has been determined that oxidative phosphorylation became functional in a hypoxic aglycemic environment despite the metabolic programming regulated by HIF-1 alpha. This data is important in determining targets for therapeutic intervention.