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We need to talk about the Warburg effect

Nature Metabolism volume 2, pages 127–129 (2020)Cite this article

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We are approaching the 100th anniversary of Otto Warburg’s first description of the metabolic phenotype bearing his name—a propensity for tumours to metabolize glucose anaerobically rather than aerobically, even when oxygen is available. Generations of scientists have studied the Warburg effect, yet misconceptions persist about its causes and relationship to oxidative metabolism in the mitochondria. Here, we review the definition of the Warburg effect and discuss its place within a modern understanding of cancer biology.

In the 1920s, Otto Warburg showed that cultured tumour tissues have high rates of glucose uptake and lactate secretion, even in the presence of oxygen (aerobic glycolysis). Those three metabolic properties—glucose uptake, lactate secretion and oxygen availability—constitute the Warburg effect as he defined it. The importance of oxygen in this definition is sometimes overlooked. Long before Warburg, Pasteur showed that oxygen suppresses the fermentation of sugars, thus identifying conversion of glucose to lactate as an expected response to hypoxia. If this logic is applied to cancer, tumours may be hypoxic, and hypoxia may induce lactate formation in tumours as it does elsewhere. But that’s not the Warburg effect. What set tumours apart in Warburg’s analysis was the lack of proportion between glycolysis and respiration—that is, the tumour samples took up glucose and converted it to lactate even when there was sufficient oxygen to convert glucose to CO2, which other tissues prefer to do and which we now know is much more productive in terms of ATP synthesis (an excellent review can be found in ref. 1).

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Fig. 1: Glycolysis and TCA-cycle metabolism supply anabolic pathways.

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Authors and Affiliations

  1. Howard Hughes Medical Institute and Children’s Medical Center Research Institute, UT Southwestern Medical Center, Dallas, TX, USA

    Ralph J. DeBerardinis

  2. Department of Medicine, Biochemistry and Molecular Genetics, Robert H. Lurie Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Navdeep S. Chandel

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  1. Ralph J. DeBerardinis
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  2. Navdeep S. Chandel
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Correspondence to Ralph J. DeBerardinis or Navdeep S. Chandel.

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Competing interests

R.J.D. is an advisor for Agios Pharmaceuticals. N.S.C. is an advisor for Rafael Pharmaceuticals.

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DeBerardinis, R.J., Chandel, N.S. We need to talk about the Warburg effect. Nat Metab 2, 127–129 (2020). https://doi.org/10.1038/s42255-020-0172-2

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