Research Spotlight: Glycolysis: Beyond energy production – A key regulator of cellular signalling and homeostasis

A recently published review from the Taylor group at UCD Conway Institute delves into the complex and evolving role of glycolysis, shifting focus from its traditional function as a central metabolic pathway for energy production, to its newly recognised roles in cellular signalling and physiological regulation.

Glycolysis, a metabolic process shared across nearly all living organisms, has long been known for its critical function in providing ATP, the primary energy currency of the cell. However, recent research has uncovered additional, previously overlooked functions of glycolytic enzymes, intermediates, and products, which go beyond simple energy generation to influence a range of cellular processes.

Pictured (L-R): Professor Cormac Taylor & Dr Sarah J Kierans

One of the key developments highlighted in this review is the identification of glycolysis as a source of important signalling molecules that help regulate cellular behavior. These molecules can affect a wide variety of cellular activities, including gene expression, protein function, and the control of cell growth and survival.

This shift in understanding underscores the multifaceted nature of glycolysis in maintaining cellular homeostasis, suggesting that the pathway plays a far broader role than initially appreciated. These new insights have opened up exciting possibilities for understanding how the control of glycolytic flux could impact cellular function in both healthy and diseased states.

The authors also address how glycolysis is co-opted by certain cell types, especially in conditions such as cancer, where altered glycolytic activity (often referred to as the Warburg effect) promotes rapid cell growth and survival. In these contexts, glycolysis does not just serve as an energy provider but also acts as a metabolic hub that supports the biosynthesis of macromolecules and other essential cellular components. The enhanced glycolytic activity in cancer cells is often linked to their ability to adapt to low-oxygen environments, resist cell death, and sustain unregulated growth.

Given the far-reaching role of glycolysis, it is important to understand how it is regulated and the physiological consequences of altering its activity. The ability to manipulate glycolytic enzymes or intermediates could have significant implications for the development of therapeutic strategies, particularly in cancer treatment, where targeting metabolic pathways could disrupt the energy balance and survival of tumor cells. Additionally, this expanded view of glycolysis could shed light on other diseases, such as metabolic disorders and neurodegenerative conditions, where cellular metabolism is disrupted.

Although glycolysis has traditionally been viewed as a key player in cellular energy metabolism, recent findings highlight its broader, more nuanced role in maintaining cellular health and function. This review offers a comprehensive examination of the new physiological and signalling functions of glycolytic components, demonstrating that glycolysis is far more than just an energy-producing pathway, and its regulation holds key insights for understanding both health and disease.

Journal Citation
Glycolysis: A multifaceted metabolic pathway and signalling hub.
Kierans SJ & Taylor CT. JBC. 2024 November. Volume 300 Issue11. doi: 10.1016/j.jbc.2024.107906