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Skp2 dictates cell cycle-dependent metabolic oscillation between glycolysis and TCA cycle
- Source :
- Cell Res
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- 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.
- Subjects :
- Cell division
Citric Acid Cycle
Cell
Oxidative phosphorylation
Biology
Article
Cell Line
S Phase
Mice
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Humans
Protein Isoforms
Glycolysis
RNA, Small Interfering
S-Phase Kinase-Associated Proteins
Molecular Biology
030304 developmental biology
0303 health sciences
Nocodazole
G1 Phase
Ubiquitination
Correction
Cell Biology
Metabolism
Cell cycle
Isocitrate Dehydrogenase
Cell biology
Citric acid cycle
Glucose
medicine.anatomical_structure
Mutagenesis, Site-Directed
Phosphorylation
RNA Interference
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 17487838 and 10010602
- Volume :
- 31
- Database :
- OpenAIRE
- Journal :
- Cell Research
- Accession number :
- edsair.doi.dedup.....afd2313347b03adb5b002efd2483b9f3