PFKM phosphorylates histone H3 and promotes mitotic progression by sensing the levels of citrate

Pianpian Lin, Yijun Qi, Huiying Chu, Hongyu Wu, Yajuan Zhang, Xiaolan Huang, Chen Li, Xiaoyan Xu, Hong Gao, Rong Zeng, Guohui Li () and Weiwei Yang ()
Additional contact information
Pianpian Lin: Shanghai Institute of Biochemistry and Cell Biology
Yijun Qi: University of Chinese Academy of Sciences
Huiying Chu: Liaoning Normal University
Hongyu Wu: Shanghai Institute of Biochemistry and Cell Biology
Yajuan Zhang: Shanghai Institute of Biochemistry and Cell Biology
Xiaolan Huang: University of Chinese Academy of Sciences
Chen Li: Shanghai Jiao Tong University School of Medicine
Xiaoyan Xu: Westlake University
Hong Gao: Shanghai Institute of Biochemistry and Cell Biology
Rong Zeng: Shanghai Institute of Biochemistry and Cell Biology
Guohui Li: Liaoning Normal University
Weiwei Yang: Shanghai Institute of Biochemistry and Cell Biology

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract Emerging evidence indicates that metabolic signals—including nutrient availability, biosynthetic intermediates, and energy balance—are linked to cell cycle progression. However, how these signals are sensed by the cell cycle machinery remains unclear. Citrate, a key intermediate in the TCA cycle, peaks during mitosis (M phase) and is detected by the glycolytic enzyme ATP-dependent 6-phosphofructokinase 1 muscle isoform (PFKM), accelerating mitotic progression. Mechanistically, citrate binds PFKM, disrupting its tetrameric structure into dimers. Dimeric PFKM interacts with nucleosomes and phosphorylates histone H3 at serine 10 (H3S10), functioning as a protein kinase to promote mitosis and cell proliferation. Structural simulations reveal that PFKM binds nucleosomes optimally when H3S10 aligns with its catalytic site. Disrupting citrate-PFKM or PFKM-H3 interactions reduces H3S10 phosphorylation, delays mitosis, and suppresses tumor growth and T-cell proliferation. Our findings demonstrate that PFKM acts as a citrate sensor, coupling metabolic signals to cell cycle regulation.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62111-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62111-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-62111-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().