RRC ID 62699
Author Shiratori R, Furuichi K, Yamaguchi M, Miyazaki N, Aoki H, Chibana H, Ito K, Aoki S.
Title Glycolytic suppression dramatically changes the intracellular metabolic profile of multiple cancer cell lines in a mitochondrial metabolism-dependent manner.
Journal Sci Rep
Abstract Most cancer cells rely on glycolysis to generate ATP, even when oxygen is available. However, merely inhibiting the glycolysis is insufficient for the eradication of cancer cells. One main reason for this is that cancer cells have the potential to adapt their metabolism to their environmental conditions. In this study, we investigated how cancer cells modify their intracellular metabolism when glycolysis is suppressed, using PANC-1 pancreatic cancer cells and two other solid tumor cell lines, A549 and HeLa. Our study revealed that glycolytically suppressed cells upregulated mitochondrial function and relied on oxidative phosphorylation (OXPHOS) to obtain the ATP necessary for their survival. Dynamic changes in intracellular metabolic profiles were also observed, reflected by the reduced levels of TCA cycle intermediates and elevated levels of most amino acids. Glutamine and glutamate were important for this metabolic reprogramming, as these were largely consumed by influx into the TCA cycle when the glycolytic pathway was suppressed. During the reprogramming process, activated autophagy was involved in modulating mitochondrial function. We conclude that upon glycolytic suppression in multiple types of tumor cells, intracellular energy metabolism is reprogrammed toward mitochondrial OXPHOS in an autophagy-dependent manner to ensure cellular survival.
Volume 9(1)
Pages 18699
Published 2019-12-10
DOI 10.1038/s41598-019-55296-3
PII 10.1038/s41598-019-55296-3
PMID 31822748
PMC PMC6904735
MeSH A549 Cells / metabolism Adenosine Triphosphate / metabolism Autophagy Cell Line, Tumor Cell Survival Citric Acid Cycle Cytoplasm / metabolism Energy Metabolism Glucose / metabolism Glycolysis / physiology* HeLa Cells / metabolism Humans Metabolome Mitochondria / metabolism* Neoplasms / metabolism* Oxidative Phosphorylation Pancreatic Neoplasms / metabolism
DNA material mitoKeima-Red (RDB18369)