Journal of Cell Biology and Metabolism

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

The Role of AMPK Signaling in Cellular Energy Sensing and Metabolic Regulation

Tom Johne*

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

*Corresponding Author:
Tom Johne
Department of Radiology
University of Harvard, Boston, USA.
E-mail: Joh@bc.iol.ethz.ch

Received: 03-Apr-2025, Manuscript No. AACBM-25-164636; Editor assigned: 04-Apr-2025, PreQC No. AACBM-25-1646365(PQ); Reviewed: 18-Apr-2025, QC No AACBM-25-1646365; Revised: 21-Apr-2025, Manuscript No. AACBM-25-1646365(R); Published: 28-Apr-2025, DOI:10.35841/aacbm-7.2.258

Citation: Johne T. The role of AMPK signaling in cellular energy sensing and metabolic regulation. J Cell Biol Metab. 2025;7(2):258.

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Introduction

AMP-activated protein kinase (AMPK) is a central energy sensor that maintains cellular energy balance by responding to changes in intracellular ATP levels. Activated under conditions of metabolic stress such as nutrient deprivation, exercise, or hypoxia, AMPK orchestrates a shift from energy-consuming anabolic pathways to energy-generating catabolic processes. Its role as a metabolic master switch enables cells to adapt to fluctuating energy demands, ensuring survival and function under challenging conditions [1, 2].

AMPK is activated when the AMP/ATP or ADP/ATP ratio increases, signaling a drop in energy availability. This activation occurs through phosphorylation at a critical threonine residue on the AMPK α-subunit, primarily by upstream kinases such as liver kinase B1 (LKB1) and calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ). Once activated, AMPK phosphorylates a wide range of downstream targets that regulate glucose uptake, lipid oxidation, autophagy, and mitochondrial biogenesis [3, 4].

In skeletal muscle, AMPK enhances glucose uptake by promoting the translocation of GLUT4 transporters to the plasma membrane and increases fatty acid oxidation by inhibiting acetyl-CoA carboxylase (ACC), thereby reducing malonyl-CoA levels and facilitating mitochondrial entry of fatty acids. In the liver, AMPK suppresses gluconeogenesis and lipogenesis by downregulating transcription factors like SREBP-1c and ChREBP. These effects help to conserve energy and prevent excessive fat accumulation, key factors in metabolic diseases [5].

Beyond acute metabolic regulation, AMPK influences long-term cellular adaptation by modulating gene expression and mitochondrial dynamics. It activates transcriptional coactivators such as PGC-1α, which drive mitochondrial biogenesis and improve oxidative metabolism. This adaptation is particularly beneficial in tissues with high energy demands, including the heart, brain, and skeletal muscle [6, 7].

AMPK also intersects with other metabolic regulators, notably mTOR and sirtuins, forming an integrated network that coordinates growth, autophagy, and aging. AMPK inhibits mTORC1, a key promoter of anabolic processes and cell proliferation, thereby acting as a checkpoint that prevents growth under energy-deficient conditions. This inhibitory relationship is crucial in contexts such as cancer, where dysregulated mTOR signaling promotes unchecked proliferation [8].

The role of AMPK in disease has gained significant attention, particularly in metabolic disorders like type 2 diabetes, obesity, and cardiovascular disease. In insulin resistance, AMPK activation improves glucose utilization and reduces hepatic glucose output, contributing to better glycemic control. Pharmacological activators of AMPK, such as metformin and AICAR, have demonstrated beneficial effects in both experimental and clinical settings, reinforcing its therapeutic potential [9].

Moreover, AMPK’s influence extends to aging and longevity. Caloric restriction, a well-established intervention for lifespan extension, activates AMPK and enhances cellular resilience. Similarly, exercise-induced AMPK activation supports metabolic health and protects against age-related decline [10].

Conclusion

In conclusion, AMPK serves as a fundamental regulator of cellular energy homeostasis, enabling cells to sense energy depletion and initiate adaptive responses. Through its broad influence on metabolism, gene expression, and cellular stress pathways, AMPK plays a vital role in maintaining physiological balance and preventing metabolic disease. Targeting the AMPK signaling pathway offers a promising strategy for therapeutic intervention across a spectrum of energy-related disorders.

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