Anti-warburg effect of melatonin: A proposed mechanism to explain its inhibition of multiple diseases

Russel J. Reiter, Ramaswamy Sharma, Sergio Rosales-Corral

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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 mitochon-dria 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.

Original languageEnglish (US)
Article number764
Pages (from-to)1-24
Number of pages24
JournalInternational journal of molecular sciences
Volume22
Issue number2
DOIs
StatePublished - Jan 2 2021

Keywords

  • Aerobic glycolysis
  • Hypoxia-inducible factor 1α
  • Mitochondrial melatonin synthesis
  • Pentose phosphate pathway
  • Pyruvate dehydrogenase complex
  • Pyruvate dehydrogenase kinase

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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