PGC-1α Signaling and Mitochondrial Metabolism in Cancer Cells

Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) sits at the nexus of transcriptional networks governing mitochondrial biogenesis, energy production and redox balance. In cancer cells, PGC-1α orchestrates adaptive programmes that allow tumours to exploit oxidative phosphorylation (OXPHOS) alongside glycolysis, thereby achieving bioenergetic plasticity under fluctuating nutrient and oxygen levels. Activation of upstream sensors such as AMP-activated protein kinase (AMPK) or cyclic AMP-dependent protein kinase (PKA) leads to post-translational modifications and increased expression of PGC-1α, which in turn co-activates nuclear receptors and transcription factors to enhance mitochondrial mass, electron transport chain capacity and antioxidant defence. Through these actions, PGC-1α influences tumour cell proliferation, survival under metabolic stress, resistance to chemotherapeutic agents and metastatic potential. Context-dependent roles have emerged: in some settings PGC-1α supports tumour suppression by restoring mitochondrial respiration, while in others it fosters metastasis and drug tolerance by upregulating fatty acid oxidation and reactive oxygen species (ROS) detoxification. A growing body of work highlights how PGC-1α-mediated reprogramming of glutamine and lipid metabolism further refines the metabolic landscape of distinct cancer types. Understanding the balance between its tumour-promoting and tumour-suppressing functions is critical for the design of therapies aimed at targeting mitochondrial metabolism in oncology.

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PGC-1α Signaling and Mitochondrial Metabolism in Cancer Cells publication trend

The graph below shows the total number of articles in pgc-1α signaling and mitochondrial metabolism in cancer cells across all publications each year (not limited to Nature Index journals).

Technical terms

PGC-1α: A transcriptional coactivator that coordinates mitochondrial biogenesis and oxidative metabolism.

Oxidative Phosphorylation (OXPHOS): Mitochondrial process generating ATP via electron transport and proton gradient.

Glycolytic Reprogramming: Shift in cellular energy production from OXPHOS to glycolysis, common in tumours.

Mitochondrial Biogenesis: Production of new mitochondria involving synthesis of mitochondrial proteins and DNA replication.

Bioenergetic Plasticity: Ability of cells to switch between metabolic pathways to meet changing energy demands.

References

1. Knockdown of PGC1α suppresses dysplastic oral keratinocytes proliferation through reprogramming energy metabolism. International Journal of Oral Science (2023).
2. Carcinoembryonic antigen potentiates non-small cell lung cancer progression via PKA-PGC-1ɑ axis. Molecular Biomedicine (2024).
3. An AMP‐activated protein kinase‐PGC‐1α axis mediates metabolic plasticity in glioblastoma. Clinical and Translational Medicine (2024).