title: Decoding Warburg's hypothesis: tumor-related mutations in the mitochondrial respiratory chain.
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.
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS), HUVR/CSIC/Universidad de Sevilla, Sevilla, Spain.|Departamento de Bioquímica Vegetal y Biología Molecular, Facultad de Biología, Sevilla, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Garcia-Heredia
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS), HUVR/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Amancio
authors.initials: A
authors.lastname: Carnero
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045222:Electron Transport Chain Complex Proteins / Q000235:genetics* / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010085:Oxidative Phosphorylation; D010641:Phenotype; D012307:Risk Factors
chemical_list: D045222:Electron Transport Chain Complex Proteins; D024101:Mitochondrial Proteins
keywords: Warburg’s hypothesis; cancer; metabolic switch; mitochondrial respiration; mitochondrial respiratory chain