Abstract
Otto Warburg observed that cancer cells derived their energy from aerobic glycolysis by converting glucose to lactate. This mechanism is in opposition to the higher energy requirements of cancer cells because oxidative phosphorylation (OxPhos) produces more ATP from glucose. Warburg hypothesized that this phenomenon occurs due to the malfunction of mitochondria in cancer cells. The rediscovery of Warburg's hypothesis coincided with the discovery of mitochondrial tumor suppressor genes that may conform to Warburg's hypothesis along with the demonstrated negative impact of HIF-1 on PDH activity and the activation of HIF-1 by oncogenic signals such as activated AKT. This work summarizes the alterations in mitochondrial respiratory chain proteins that have been identified and their involvement in cancer. Also discussed is the fact that most of the mitochondrial mutations have been found in homoplasmy, indicating a positive selection during tumor evolution, thereby supporting their causal role.
Highlights
At the beginning of the last century, Otto Warburg observed that cancer cells based their energy production on fermentation rather than oxidation, even in the presence of oxygen; these cells utilize aerobic glycolysis to derive energy from the conversion of glucose to lactate [1,2,3]
This metabolic switch from aerobic glucose metabolism through the respiratory chain to aerobic glycolysis is typical of cancer cells, and was named the Warburg effect in honor of its discoverer
The hypoxic conditions that are present in many solid tumors may not satisfy their requirements for oxygen, permitting the cancer cells to switch off oxidative phosphorylation (OxPhos) and favor activation of glycolysis
Summary
At the beginning of the last century, Otto Warburg observed that cancer cells based their energy production on fermentation rather than oxidation, even in the presence of oxygen; these cells utilize aerobic glycolysis to derive energy from the conversion of glucose to lactate [1,2,3]. C9T cells, which have the m.12418insA mutation in homoplasmy, exhibited the lowest tumorigenic properties, showing that, in this case, heteroplasmic conditions constitute an advantage for tumor growth [61]. Cells with mutations in mtND6 contained a non-functional Complex I and an upregulated HIF-1a, VEGF and MCL-1, all of which were associated with increased tumorigenicity.
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