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Review

Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases

1
Department of Cell Systems & Anatomy, Joe R. and Teresa Lozano Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229, USA
2
Centro de Investigacion Biomedica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco CP45150, Mexico
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(2), 764; https://doi.org/10.3390/ijms22020764
Received: 14 December 2020 / Revised: 4 January 2021 / Accepted: 11 January 2021 / Published: 14 January 2021
(This article belongs to the Special Issue Molecular Research on Mitochondrial Dysfunction)
Glucose is an essential nutrient for every cell but its metabolic fate depends on cellular phenotype. Normally, the product of cytosolic glycolysis, pyruvate, is transported into mitochondria and irreversibly converted to acetyl coenzyme A by pyruvate dehydrogenase complex (PDC). In some pathological cells, however, pyruvate transport into the mitochondria is blocked due to the inhibition of PDC by pyruvate dehydrogenase kinase. This altered metabolism is referred to as aerobic glycolysis (Warburg effect) and is common in solid tumors and in other pathological cells. Switching from mitochondrial oxidative phosphorylation to aerobic glycolysis provides diseased cells with advantages because of the rapid production of ATP and the activation of pentose phosphate pathway (PPP) which provides nucleotides required for elevated cellular metabolism. Molecules, called glycolytics, inhibit aerobic glycolysis and convert cells to a healthier phenotype. Glycolytics often function by inhibiting hypoxia-inducible factor-1α leading to PDC disinhibition allowing for intramitochondrial conversion of pyruvate into acetyl coenzyme A. Melatonin is a glycolytic which converts diseased cells to the healthier phenotype. Herein we propose that melatonin’s function as a glycolytic explains its actions in inhibiting a variety of diseases. Thus, the common denominator is melatonin’s action in switching the metabolic phenotype of cells. View Full-Text
Keywords: aerobic glycolysis; mitochondrial melatonin synthesis; hypoxia-inducible factor 1α; pentose phosphate pathway; pyruvate dehydrogenase kinase; pyruvate dehydrogenase complex aerobic glycolysis; mitochondrial melatonin synthesis; hypoxia-inducible factor 1α; pentose phosphate pathway; pyruvate dehydrogenase kinase; pyruvate dehydrogenase complex
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MDPI and ACS Style

Reiter, R.J.; Sharma, R.; Rosales-Corral, S. Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases. Int. J. Mol. Sci. 2021, 22, 764. https://doi.org/10.3390/ijms22020764

AMA Style

Reiter RJ, Sharma R, Rosales-Corral S. Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases. International Journal of Molecular Sciences. 2021; 22(2):764. https://doi.org/10.3390/ijms22020764

Chicago/Turabian Style

Reiter, Russel J., Ramaswamy Sharma, and Sergio Rosales-Corral. 2021. "Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases" International Journal of Molecular Sciences 22, no. 2: 764. https://doi.org/10.3390/ijms22020764

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