EditorialEditorial

The Warburg effect drives dedifferentiation through epigenetic reprogramming

Haowen Jiang, Mohamed Jedoui and Jiangbin Ye
Cancer Biology & Medicine December 2023, 20 (12) 891-897; DOI: https://doi.org/10.20892/j.issn.2095-3941.2023.0467

Article Figures & Data

Figures

  • Otto H. Warburg and the Otto-Warburg-Haus. (A) Otto Heinrich Warburg (October 8, 1883–August 1, 1970), German biochemist and cell physiologist, is best known for his discovery of the Warburg effect. The photo is courtesy of Florian Spillert and Susanne Uebele from the Archives of the Max Planck Society. (B) The Otto-Warburg-Haus, originally founded by Warburg in 1930 as the Kaiser Wilhelm Institute for Cell Physiology, underwent a conversion to become the Archive of the Max Planck Society in 1975, after Warburg’s passing. The Archive of the Max Planck Society is located at Boltzmannstraße 14, 14195 Berlin-Dahlem, Germany. (C) Warburg’s Nobel Prize diploma, stored at the Archive of the Max Planck Society. In 1931, Warburg received the Nobel Prize in Physiology as the sole laureate, recognized for his seminal discovery of the nature and mode of action of the respiratory enzyme. (B) and (C) During a personal pilgrimage to Dahlem in May 2023, J.Y. took these photographs.
    Figure 1

    Otto H. Warburg and the Otto-Warburg-Haus. (A) Otto Heinrich Warburg (October 8, 1883–August 1, 1970), German biochemist and cell physiologist, is best known for his discovery of the Warburg effect. The photo is courtesy of Florian Spillert and Susanne Uebele from the Archives of the Max Planck Society. (B) The Otto-Warburg-Haus, originally founded by Warburg in 1930 as the Kaiser Wilhelm Institute for Cell Physiology, underwent a conversion to become the Archive of the Max Planck Society in 1975, after Warburg’s passing. The Archive of the Max Planck Society is located at Boltzmannstraße 14, 14195 Berlin-Dahlem, Germany. (C) Warburg’s Nobel Prize diploma, stored at the Archive of the Max Planck Society. In 1931, Warburg received the Nobel Prize in Physiology as the sole laureate, recognized for his seminal discovery of the nature and mode of action of the respiratory enzyme. (B) and (C) During a personal pilgrimage to Dahlem in May 2023, J.Y. took these photographs.

  • The Warburg effect and metabolic rewiring. The Warburg effect arises due to impaired mitochondrial function, which significantly affects key metabolic processes. Mitochondria, which are crucial for ATP synthesis, NAD+ regeneration, the synthesis of macromolecules and epigenetic regulations, become dysfunctional when the electron transport chain (ETC) is inhibited. As a consequence, cells undergo adaptive changes, increasingly depend on glycolysis to produce ATP, modify various pathways for NAD+ regeneration, and remodel the epigenome by altering the levels of some metabolites.
    Figure 2

    The Warburg effect and metabolic rewiring. The Warburg effect arises due to impaired mitochondrial function, which significantly affects key metabolic processes. Mitochondria, which are crucial for ATP synthesis, NAD+ regeneration, the synthesis of macromolecules and epigenetic regulations, become dysfunctional when the electron transport chain (ETC) is inhibited. As a consequence, cells undergo adaptive changes, increasingly depend on glycolysis to produce ATP, modify various pathways for NAD+ regeneration, and remodel the epigenome by altering the levels of some metabolites.

  • The primary target of mitochondrial uncoupler. The mitochondrial electron transport chain (ETC) generates ATP through a proton gradient formed during substrate oxidation. When ATP synthesis slows down, the proton gradient builds up, inhibiting the ETC and NADH oxidation. To reactivate ETC, it is crucial to decrease the proton gradient. Mitochondrial uncouplers achieve this by dissipating the gradient. Figures 2 and 3 were generated using BioRender.
    Figure 3

    The primary target of mitochondrial uncoupler. The mitochondrial electron transport chain (ETC) generates ATP through a proton gradient formed during substrate oxidation. When ATP synthesis slows down, the proton gradient builds up, inhibiting the ETC and NADH oxidation. To reactivate ETC, it is crucial to decrease the proton gradient. Mitochondrial uncouplers achieve this by dissipating the gradient. Figures 2 and 3 were generated using BioRender.

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