Journal
ONCOTARGET
Volume 6, Issue 39, Pages 41582-41599Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.6057
Keywords
cancer; metabolic switch; Warburg's hypothesis; mitochondrial respiration; mitochondrial respiratory chain
Categories
Funding
- Spanish Ministry of Economy and Competitiveness
- Plan Nacional de I+D+I
- Plan Estatal de I+D+I
- ISCIII [Fis: PI12/00137, PI15/00045, RTICC: RD12/0036/0028]
- FEDER from Regional Development European Funds (European Union)
- Consejeria de Ciencia e Innovacion [CTS-6844, CTS-1848]
- Consejeria de Salud of the Junta de Andalucia [PI-0135-2010, PI-0306-2012, PI-0096-2014]
- FEDER funds
- ISCIII
- Plan Estatal de I+D+i [PIE13/0004]
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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.
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