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Comment
. 2023 May 18;83(10):1549-1551.
doi: 10.1016/j.molcel.2023.04.013.

Lactate fuels mitosis

Xiaoming Dai  1 , Wenyi Wei  2
Affiliations
Comment

Lactate fuels mitosis

Xiaoming Dai et al. Mol Cell. .

Abstract

Cell cycle and metabolism are intimately intertwined, but how metabolites directly regulate cell-cycle machinery remains elusive. Liu et al.1 reveal that glycolysis end-product lactate directly binds and inhibits the SUMO protease SENP1 to govern the E3 ligase activity of the anaphase-promoting complex, leading to efficient mitotic exit in proliferative cells.

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Conflict of interest statement

Declaration of interests W.W. is a co-founder and consultant for ReKindle Therapeutics.

Figures

Figure 1.
Figure 1.. A working model of how lactate regulates mitosis by modulating the APC/C complex activity.
When lactate level is low at G1/S phase, it cannot efficiently inhibit SENP1’s enzymatic activity to suppress the SUMOylation of APC4, leading to cyclin B1 and securin accumulation before mitosis. After lactate levels increase at G2/M phase, it binds and inhibits SENP1 by forming a complex with zinc, leading to the stabilization of APC4 SUMOylation, which promotes UBE2C binding towards APC/C to timely degrade cyclin B1 and securin and modulate mitosis. This figure was created with BioRender.com.
See this image and copyright information in PMC

Comment on

  • Lactate regulates cell cycle by remodelling the anaphase promoting complex.
    Liu W, Wang Y, Bozi LHM, Fischer PD, Jedrychowski MP, Xiao H, Wu T, Darabedian N, He X, Mills EL, Burger N, Shin S, Reddy A, Sprenger HG, Tran N, Winther S, Hinshaw SM, Shen J, Seo HS, Song K, Xu AZ, Sebastian L, Zhao JJ, Dhe-Paganon S, Che J, Gygi SP, Arthanari H, Chouchani ET. Liu W, et al. Nature. 2023 Apr;616(7958):790-797. doi: 10.1038/s41586-023-05939-3. Epub 2023 Mar 15. Nature. 2023. PMID: 36921622 Free PMC article.

References

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