Regulative Roles of Metabolic Plasticity Caused by Mitochondrial Oxidative Phosphorylation and Glycolysis on the Initiation and Progression of Tumorigenesis

Sep 24, 2026

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One important feature of tumour development is the regulatory role of metabolic plasticity that maintains the balance between mitochondrial oxidative phosphorylation and glycolysis in cancer cells. Recent work has focused on how tumour cells transition between and/or execute mitochondrial oxidative phosphorylation and glycolysis programs. This review summarizes key traits of metabolic plasticity, highlighting effects on immune escape, angiogenesis, migration, invasiveness, heterogeneity, adhesion, and related cancer phenotypes across tumour initiation and progression. It provides an integrated view of how abnormal metabolic remodeling drives malignant proliferation and pathophysiological changes in carcinoma.

LanguageEnglish

CategoryHealthcare

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Pages44

Reading Time1 h 51 min

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Abstract

Keywords

Introduction

Warburg effect and metabolic differences

ATP production balance: OXPHOS versus glycolysis

Metabolic plasticity in tumourigenesis

Review Regulative Roles of Metabolic Plasticity Caused by Mitochondrial Oxidative Phosphorylation and Glycolysis on the Initiation and Progression of Tumorigenesis Nan Niu 1,2, Jinfeng Ye 1, Zhangli Hu 1, Junbin Zhang 1 and Yun Wang 1, * Citation: Niu, N.; Ye, J.; Hu, Z.; Zhang, J.; Wang, Y. Regulative Roles of Metabolic Plasticity Caused by Mitochondrial Oxidative Phosphorylation and Glycolysis on the Initiation and Progression of Tumorigenesis. Int. J. Mol. Sci. 2023, 24, 7076. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms24087076 Academic Editors: Andrea Disanza and Iain P. Hargreaves Received: 3 February 2023 Revised: 23 March 2023 Accepted: 4 April 2023 Published: 11 April 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Shenzhen Engineering Labortaory for Marine Algal Biotechnology, Longhua Innovation Institute for Biotechnology, College of Life Sciences and Oceanography, Lihu Campus of Shenzhen University, Shenzhen 518055, China; nn2023ﬂ[y@szu.edu.cn](y@szu.edu.cn) (N.N.) 2 College of Physics and Optoelectronic Engineering, Canghai Campus of Shenzhen University, Shenzhen 518060, China * [Correspondence: yunw@szu.edu.cn](Correspondence: yunw@szu.edu.cn); Tel.: +86-755-2695-8895 Abstract: One important feature of tumour development is the regulatory role of metabolic plasticity in maintaining the balance of mitochondrial oxidative phosphorylation and glycolysis in cancer cells. In recent years, the transition and/or function of metabolic phenotypes between mitochondrial oxidative phosphorylation and glycolysis in tumour cells have been extensively studied. In this review, we aimed to elucidate the characteristics of metabolic plasticity (emphasizing their effects, such as immune escape, angiogenesis migration, invasiveness, heterogeneity, adhesion, and phenotypic properties of cancers, among others) on tumour progression, including the initiation and progression phases. Thus, this article provides an overall understanding of the inﬂuence of abnormal metabolic remodeling on malignant proliferation and pathophysiological changes in carcinoma. Keywords: tumorigenesis; glycolysis; mitochondrial oxidative phosphorylation; metabolic plasticity; malignant proliferation 1. Introduction The energy metabolism of normal cells is maintained in a balanced state. In the presence of oxygen, partial metabolites are transmitted through respiratory chain enzyme complexes I–IV on the inner membrane of mitochondria, and adenosine triphosphates (ATPs) are ﬁnally synthesized by oxidative phosphorylation of adenosine triphosphate synthase (ATPase) [1–3], which only occupies a small part of the whole cell energy supply. More glycolysis-related enzymes are activated when cells are exposed to ischaemia and hypoxia to maintain the cellular energy supply [4] . However, in the 1920s, Otto Warburg's pioneering study demonstrated that, unlike normal cells, which produce energy by oxidative phosphorylation of mitochondria, tumour cells mainly produce energy through glycolysis, even if the oxygen supply is sufﬁcient [5] . This abnormal metabolic status in tumour cells is called the Warburg Effect, which is the most signiﬁcant metabolic difference between normal and tumour cells. The Warburg Effect is responsible for various characteristics associated with the occurrence and development of tumour cells, such as their phenotype, material metabolism, molecular regulation, proliferation, invasion, immune escape, and angiogenesis stimulation [6–10] . Typically, in the presence of oxygen, glycolysis produces only two ATPs per glucose molecule, which is much lower than the ~

FAQs

What is metabolic plasticity in cancer cells, and what balance does it regulate?

Metabolic plasticity refers to the ability of tumour cells to coordinate glycolysis and mitochondrial oxidative phosphorylation. It helps maintain a balance between these two metabolic states during tumour development.

What is the Warburg Effect and why is it important for tumourigenesis?

The Warburg Effect is the observation that tumour cells mainly generate energy via glycolysis even when oxygen is sufficient. It is linked to multiple tumour cell traits such as proliferation, invasion, immune escape, and angiogenesis stimulation.

How do tumour cells use glycolysis and mitochondrial oxidative phosphorylation under different conditions?

Although glycolysis contributes fewer ATPs per glucose than oxidative phosphorylation, tumour cells can shift to use mitochondrial oxidative phosphorylation under specific conditions. This adjustment depends on factors such as abnormal phenotype, functional transformation, and internal or external stimuli.

Sep 24, 2026

Uploaded by Himbo