Skp2 dictates cell cycle-dependent metabolic oscillation between glycolysis and TCA cycle

Jing Liu, Yunhua Peng, Le Shi, Lixin Wan, Hiroyuki Inuzuka, Jiangang Long, Jianping Guo, Jinfang Zhang, Min Yuan, Shuangxi Zhang, Xun Wang, Jing Gao, Xiangpeng Dai, Shozo Furumoto, Lijun Jia, Pier Paolo Pandolfi, John M. Asara, William G. Kaelin, Jiankang Liu, Wenyi Wei

研究成果: Article査読

18 被引用数 (Scopus)


Whether glucose is predominantly metabolized via oxidative phosphorylation or glycolysis differs between quiescent versus proliferating cells, including tumor cells. However, how glucose metabolism is coordinated with cell cycle in mammalian cells remains elusive. Here, we report that mammalian cells predominantly utilize the tricarboxylic acid (TCA) cycle in G1 phase, but prefer glycolysis in S phase. Mechanistically, coupling cell cycle with metabolism is largely achieved by timely destruction of IDH1/2, key TCA cycle enzymes, in a Skp2-dependent manner. As such, depleting SKP2 abolishes cell cycle-dependent fluctuation of IDH1 protein abundance, leading to reduced glycolysis in S phase. Furthermore, elevated Skp2 abundance in prostate cancer cells destabilizes IDH1 to favor glycolysis and subsequent tumorigenesis. Therefore, our study reveals a mechanistic link between two cancer hallmarks, aberrant cell cycle and addiction to glycolysis, and provides the underlying mechanism for the coupling of metabolic fluctuation with periodic cell cycle in mammalian cells.

ジャーナルCell Research
出版ステータスPublished - 2021 1月

ASJC Scopus subject areas

  • 分子生物学
  • 細胞生物学


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