Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer
Oxidative and glycolytic metabolism produce energy in the form of ATP and produce intermediates for biomass production. Oxidative metabolism predominates under normoxic conditions and in quiescent or slowly proliferating cells. On the other hand, under hypoxic or pseudohypoxic conditions and in rapi...
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2025-07-01
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| author | Marco Cordani Cristiano Rumio Giulio Bontempi Raffaele Strippoli Fabrizio Marcucci |
| author_facet | Marco Cordani Cristiano Rumio Giulio Bontempi Raffaele Strippoli Fabrizio Marcucci |
| author_sort | Marco Cordani |
| collection | DOAJ |
| description | Oxidative and glycolytic metabolism produce energy in the form of ATP and produce intermediates for biomass production. Oxidative metabolism predominates under normoxic conditions and in quiescent or slowly proliferating cells. On the other hand, under hypoxic or pseudohypoxic conditions and in rapidly proliferating cells, glycolysis becomes the predominant pathway. The balance between oxidative and glycolytic metabolism is finely tuned in physiological conditions and becomes dysregulated in many pathological conditions, most notably cancer. In this article we summarize the evidence that has been gathered over the last few years on the mechanisms underlying this balance and the consequences of their dysregulation. We discuss first the non-metabolic factors (mitochondria, cell cycle, cell type, tissue type), then molecules that are at the intersection between glycolytic and oxidative metabolism and those molecules that are inherent to oxidative or glycolytic metabolism that affect the equilibrium between the two energy-producing pathways. Eventually, we discuss pharmacologic or genetic means that allow manipulating this equilibrium. As will be seen, lactic acidosis has taken center stage in this field and lactate has been shown to fuel oxidative metabolism. This suggests that if glycolytic metabolism predominates, as has often been shown in cancer, mechanisms come into work that reestablish a metabolic heterogeneity. Thus, while one pathway may be predominant over the other, it seems as if fail-safe mechanisms are at work that avoid the possibility that it becomes the only energy-producing pathway. Eventually, we discuss possible therapeutic consequences that may derive from this expanding knowledge, in particular, as regards tumor therapy. |
| format | Article |
| id | doaj-art-1ddf6779ed734ff08717d63a7191b2da |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-1ddf6779ed734ff08717d63a7191b2da2025-08-20T03:36:03ZengMDPI AGCells2073-44092025-07-011415117710.3390/cells14151177Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in CancerMarco Cordani0Cristiano Rumio1Giulio Bontempi2Raffaele Strippoli3Fabrizio Marcucci4Department of Biochemistry and Molecular Biology, Faculty of Biological Sciences, Complutense University of Madrid, 28040 Madrid, SpainDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Via Trentacoste 2, 20134 Milan, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, ItalyDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Via Trentacoste 2, 20134 Milan, ItalyOxidative and glycolytic metabolism produce energy in the form of ATP and produce intermediates for biomass production. Oxidative metabolism predominates under normoxic conditions and in quiescent or slowly proliferating cells. On the other hand, under hypoxic or pseudohypoxic conditions and in rapidly proliferating cells, glycolysis becomes the predominant pathway. The balance between oxidative and glycolytic metabolism is finely tuned in physiological conditions and becomes dysregulated in many pathological conditions, most notably cancer. In this article we summarize the evidence that has been gathered over the last few years on the mechanisms underlying this balance and the consequences of their dysregulation. We discuss first the non-metabolic factors (mitochondria, cell cycle, cell type, tissue type), then molecules that are at the intersection between glycolytic and oxidative metabolism and those molecules that are inherent to oxidative or glycolytic metabolism that affect the equilibrium between the two energy-producing pathways. Eventually, we discuss pharmacologic or genetic means that allow manipulating this equilibrium. As will be seen, lactic acidosis has taken center stage in this field and lactate has been shown to fuel oxidative metabolism. This suggests that if glycolytic metabolism predominates, as has often been shown in cancer, mechanisms come into work that reestablish a metabolic heterogeneity. Thus, while one pathway may be predominant over the other, it seems as if fail-safe mechanisms are at work that avoid the possibility that it becomes the only energy-producing pathway. Eventually, we discuss possible therapeutic consequences that may derive from this expanding knowledge, in particular, as regards tumor therapy.https://www.mdpi.com/2073-4409/14/15/1177glycolysisoxidative metabolismregulationcancerlactic acidosis |
| spellingShingle | Marco Cordani Cristiano Rumio Giulio Bontempi Raffaele Strippoli Fabrizio Marcucci Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer Cells glycolysis oxidative metabolism regulation cancer lactic acidosis |
| title | Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer |
| title_full | Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer |
| title_fullStr | Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer |
| title_full_unstemmed | Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer |
| title_short | Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer |
| title_sort | oxidative and glycolytic metabolism their reciprocal regulation and dysregulation in cancer |
| topic | glycolysis oxidative metabolism regulation cancer lactic acidosis |
| url | https://www.mdpi.com/2073-4409/14/15/1177 |
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