Journal of Cell Biology and Metabolism

All submissions of the EM system will be redirected to Online Manuscript Submission System. Authors are requested to submit articles directly to Online Manuscript Submission System of respective journal.
Reach Us +1 (202) 780-3397

Brief Report - Journal of Cell Biology and Metabolism (2025) Volume 7, Issue 2

Molecular Crosstalk Between Cell Cycle Regulators and Metabolic Enzymes

Paui De*

Department of Radiology, University of Harvard, Boston, USA.

*Corresponding Author:
Paui De
Department of Radiology
University of Harvard, Boston, USA.
E-mail: de@cm.ac.uk

Received: 03-Apr-2025, Manuscript No. AACBM-25-164642; Editor assigned: 04-Apr-2025, PreQC No. AACBM-25-1646425(PQ); Reviewed: 18-Apr-2025, QC No AACBM-25-1646425; Revised: 21-Apr-2025, Manuscript No. AACBM-25-1646425(R); Published: 28-Apr-2025, DOI:10.35841/aacbm-7.2.263

Citation: De P. Molecular crosstalk between cell cycle regulators and metabolic enzymes. J Cell Biol Metab. 2025;7(2):263.

Visit for more related articles at Journal of Cell Biology and Metabolism

Introduction

The coordination between cell proliferation and metabolism is essential for maintaining cellular and organismal homeostasis. Traditionally, the cell cycle and metabolic pathways were studied as distinct processes—one governing cell division and the other managing energy production and biosynthesis. However, accumulating evidence reveals a complex molecular crosstalk between cell cycle regulators and metabolic enzymes, highlighting a tightly interwoven network where each influences the other. This interplay ensures that cells only progress through the cell cycle when metabolic conditions are optimal and that metabolism adjusts to meet the biosynthetic demands of proliferation [1, 2].

Central to this coordination are cyclin-dependent kinases (CDKs), which orchestrate the sequential progression through cell cycle phases. These kinases, in association with their cyclin partners, regulate not only cell cycle transitions but also directly influence metabolic enzymes. For instance, CDK1 and CDK4 have been shown to phosphorylate key metabolic regulators, thereby modulating pathways such as glycolysis, glutaminolysis, and lipid synthesis. This integration allows proliferating cells to synchronize cell division with the availability of metabolic substrates and energy [3, 4].

Glycolytic flux is often upregulated during the cell cycle, particularly at the G1/S transition, where cells commit to DNA replication. CDK4/6-cyclin D complexes have been implicated in enhancing the expression of glycolytic genes through downstream effectors like E2F transcription factors. Moreover, enzymes such as hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2) are subject to cell cycle-dependent regulation, ensuring the timely production of ATP and metabolic intermediates required for nucleotide and amino acid synthesis [5, 6].

Similarly, the tricarboxylic acid (TCA) cycle and mitochondrial metabolism are influenced by cell cycle progression. CDK1 can localize to mitochondria during mitosis, phosphorylating mitochondrial proteins to boost ATP production in support of mitotic processes. This illustrates how energy generation is ramped up at critical cell cycle phases to meet increased demands [7].

Conversely, metabolic enzymes can also influence cell cycle progression. Metabolic sensors such as AMP-activated protein kinase (AMPK) and the mechanistic target of rapamycin (mTOR) integrate nutrient and energy signals to control cell cycle entry. When energy is scarce, AMPK activation inhibits mTOR and downregulates cyclin expression, halting cell cycle progression to conserve resources. In contrast, high nutrient availability activates mTOR, promoting anabolic processes and cell growth, thus facilitating progression through the cell cycle [8].

Oncogenic transformations often exploit this crosstalk by rewiring both metabolic and cell cycle pathways to support uncontrolled proliferation. Mutations in tumor suppressors such as p53 and RB disrupt normal cell cycle control and alter metabolism to favor aerobic glycolysis (the Warburg effect). Moreover, overexpression of c-Myc not only drives cell cycle progression but also enhances glutamine metabolism and nucleotide biosynthesis, enabling rapid cell growth and division [9].

This bidirectional regulation between cell cycle machinery and metabolism also plays a role in stem cell maintenance, immune responses, and tissue regeneration, where precise control of proliferation and metabolic state is required. In stem cells, for example, shifts between quiescence and proliferation are accompanied by metabolic remodeling, and disruptions in this balance can lead to developmental disorders or cancer.

Targeting the molecular nodes at the interface of the cell cycle and metabolism has emerged as a promising strategy in cancer therapy. CDK inhibitors, already in clinical use, may achieve enhanced efficacy when combined with metabolic modulators. For instance, simultaneous inhibition of CDK4/6 and glycolytic pathways has shown synergistic effects in preclinical models of breast cancer [10].

Conclusion

In conclusion, the molecular crosstalk between cell cycle regulators and metabolic enzymes forms a dynamic regulatory circuit that ensures cellular proliferation is matched with metabolic capability. This coordination is vital for normal cell function and, when disrupted, contributes to the development of disease. Understanding and manipulating this intersection provides valuable insights into cell biology and opens new avenues for therapeutic intervention in cancer and metabolic disorders.

References

  1. Seo J, Park M. Molecular crosstalk between cancer and neurodegenerative diseases. Cell Mol Life Sci. 2020;77(14):2659-80.

    2. Indexed at, Google Scholar, Cross Ref

  2. Vanden Berghe T, Kaiser WJ, Bertrand MJ, et al. Molecular crosstalk between apoptosis, necroptosis, and survival signaling. Molecular & cellular oncology. 2015;2(4):e975093.

    3. Indexed at, Google Scholar, Cross Ref

  3. Salzet M, Capron A, Stefano GB. Molecular Crosstalk in Host–Parasite Relationships:: Schistosome–and Leech–Host Interactions. Parasitology Today. 2000;16(12):536-40.

    4. Indexed at, Google Scholar, Cross Ref

  4. Hakeem KR, Rehman RU, Tahir I, et al. Plant signaling: understanding the molecular crosstalk. Springer India; 2014.

    5. Indexed at, Google Scholar, Cross Ref

  5. Göhre V, Jones AM, Sklenár J, et al. Molecular crosstalk between PAMP-triggered immunity and photosynthesis. Molecular Plant-Microbe Interactions. 2012;25(8):1083-92.

    6. Indexed at, Google Scholar, Cross Ref

  6. Sansonetti P. Host–pathogen interactions: the seduction of molecular cross talk. Gut. 2002;50(suppl 3):iii2-8.

    7. Indexed at, Google Scholar, Cross Ref

  7. Chen X, Gumbiner BM. Crosstalk between different adhesion molecules. Current opinion in cell biology. 2006;18(5):572-8.

    8. Indexed at, Google Scholar, Cross Ref

  8. Sanz-Pamplona R, Berenguer A, Cordero D, et al. Aberrant gene expression in mucosa adjacent to tumor reveals a molecular crosstalk in colon cancer. Mol cancer. 2014;13:1-9.

    9. Indexed at, Google Scholar, Cross Ref

  9. Lehman JA, Gomez-Cambronero J. Molecular crosstalk between p70S6k and MAPK cell signaling pathways. Biochem Biophys Res Commun. 2002;293(1):463-9.

    10. Indexed at, Google Scholar, Cross Ref

  10. Liu H, Timko MP. Jasmonic acid signaling and molecular crosstalk with other phytohormones. Int J Mol Sci. 2021;22(6):2914.

    11. Indexed at, Google Scholar, Cross Ref

Get the App