RT Journal Article SR Electronic T1 Aerobic glycolysis in cancer cells supplies ATP while preventing excess metabolic thermogenesis JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.11.16.468557 DO 10.1101/2021.11.16.468557 A1 Nobuyuki Okahashi A1 Tomoki Shima A1 Yuya Kondo A1 Chie Araki A1 Shuma Tsuji A1 Akane Sawai A1 Hikaru Uehara A1 Susumu Kohno A1 Hiroshi Shimizu A1 Chiaki Takahashi A1 Fumio Matsuda YR 2021 UL http://biorxiv.org/content/early/2021/11/19/2021.11.16.468557.abstract AB A general feature of cancer metabolism is ATP regeneration via substrate-level phosphorylation even under normoxic conditions (aerobic glycolysis). However, it is unclear why cancer cells prefer the inefficient aerobic glycolysis over the highly efficient process of oxidative phosphorylation for ATP regeneration. Here, we show that a beneficial aspect of aerobic glycolysis is that it reduces metabolic heat generation during ATP regeneration. 13C-metabolic flux analysis of 12 cultured cancer cell lines and in silico metabolic simulation revealed that metabolic heat production during ATP regeneration via aerobic glycolysis was considerably lesser than that produced via oxidative phosphorylation. The dependency on aerobic glycolysis was partly alleviated upon culturing under low temperatures. In conclusion, thermogenesis is required for maintaining thermal homeostasis and can govern aerobic glycolysis in cancer cells.Competing Interest StatementThe authors have declared no competing interest.