Oxygen and Iron Availability Shapes Metabolic Adaptations of Cancer Cells

World J Oncol. 2024 Feb;15(1):28-37. doi: 10.14740/wjon1739. Epub 2024 Jan 10.

Abstract

The dynamic changes between glycolysis and oxidative phosphorylation (OXPHOS) for adenosine triphosphate (ATP) output, along with glucose, glutamine, and fatty acid utilization, etc., lead to the maintenance and selection of growth advantageous to tumor cell subgroups in an environment of iron starvation and hypoxia. Iron plays an important role in the three major biochemical reactions in nature: photosynthesis, nitrogen fixation, and oxidative respiration, which all require the participation of iron-sulfur proteins, such as ferredoxin, cytochrome b, and the complex I, II, III in the electron transport chain, respectively. Abnormal iron-sulfur cluster synthesis process or hypoxia will directly affect the function of mitochondrial electron transfer and mitochondrial OXPHOS. More research results have indicated that iron metabolism, oxygen availability and hypoxia-inducible factor mutually regulate the shift between glycolysis and OXPHOS. In this article, we make a perspective review to provide novel opinions of the regulation of glycolysis and OXPHOS in tumor cells.

Keywords: Glycolysis; Iron; Metabolism; OXPHOS; Oxygen; Tumor.

Publication types

  • Review

Grants and funding

Rui Wang is founded by China Scholarship Council (202206920039). This research was supported by funds from Natural Science Foundation of Suqian Science and Technology Bureau (K201903, Z2018076, Z2018213 and Z2022065). Jiangsu Association for Science and Technology (JSTJ-2022-004).