Abstract
Cancer cells display abnormal morphology, chromosomes, and metabolism. This review will focus on the metabolism of tumor cells integrating the available data by way of a functional approach. The first part contains a comprehensive introduction to bioenergetics, mitochondria, and the mechanisms of production and degradation of reactive oxygen species. This will be followed by a discussion on the oxidative metabolism of tumor cells including the morphology, biogenesis, and networking of mitochondria. Tumor cells overexpress proteins that favor fission, such as GTPase dynamin-related protein 1 (Drp1). The interplay between proapoptotic members of the Bcl-2 family that promotes Drp 1-dependent mitochondrial fragmentation and fusogenic antiapoptotic proteins such as Opa-1 will be presented. It will be argued that contrary to the widespread belief that in cancer cells, aerobic glycolysis completely replaces oxidative metabolism, a misrepresentation of Warburg's original results, mitochondria of tumor cells are fully viable and functional. Cancer cells also carry out oxidative metabolism and generally conform to the orthodox model of ATP production maintaining as well an intact electron transport system. Finally, data will be presented indicating that the key to tumor cell survival in an ROS rich environment depends on the overexpression of antioxidant enzymes and high levels of the nonenzymatic antioxidant scavengers.
Highlights
Every biochemical reaction within living cells involves the transduction of some degree of free energy that is derived from the oxidation of dietary nutrients
In the context of cancer, International Journal of Cell Biology when cells that use glucose as the main substrate to drive adenosine triphosphate (ATP) synthesis are subjected to hypoxia, as happens to the cells located in the center of the tumor mass, glucose uptake and metabolism increase significantly in order to maintain cellular ATP levels
The point that should be stressed here regarding the main difference between Crabtree and Warburg effects is that in the former the oxidative phosphorylation is rapidly and reversibly downregulated by the repressive effect of glucose, whereas in the latter, there is a long-lasting irreversible effect favoring fermentation due to the increased expression of proteins involved in glucose transport and metabolism [5]
Summary
Every biochemical reaction within living cells involves the transduction of some degree of free energy that is derived from the oxidation of dietary nutrients. During the sequential redox reactions of electrons transport along the ETS to their final acceptor, molecular oxygen, a significant part of the energy is conserved as protons are transported from the mitochondrial matrix to the intermembrane space, generating the Δp, at the complexes I, III, and IV.
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