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Mitochondrial and Nuclear Genes of Mitochondrial Components in Cancer
Although the observation of aerobic glycolysis of tumor cells by Otto v. Warburg had demonstrated abnormalities of mitochondrial energy metabolism in cancer decades ago, there was no clear evidence for a functional role of mutant mitochondrial proteins in cancer development until the early years of...
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Formato: | Texto |
Lenguaje: | English |
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Bentham Science Publishers Ltd.
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2709939/ https://www.ncbi.nlm.nih.gov/pubmed/19949549 http://dx.doi.org/10.2174/138920209788488517 |
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author | Kirches, E |
author_facet | Kirches, E |
author_sort | Kirches, E |
collection | PubMed |
description | Although the observation of aerobic glycolysis of tumor cells by Otto v. Warburg had demonstrated abnormalities of mitochondrial energy metabolism in cancer decades ago, there was no clear evidence for a functional role of mutant mitochondrial proteins in cancer development until the early years of the 21(st) century. In the year 2000, a major breakthrough was achieved by the observation, that several genes coding for subunits of the respiratory chain (ETC) complex II, succinate dehydrogenase (SDH) are tumor suppressor genes in heritable paragangliomas, fulfilling Knudson’s classical two-hit hypothesis. A functional inactivation of both alleles by germline mutations and chromosomal losses in the tumor tissue was found in the patients. Later, SDH mutations were also identified in sporadic paragangliomas and pheochromocytomas. Genes of the mitochondrial ATP-synthase and of mitochondrial iron homeostasis have been implicated in cancer development at the level of cell culture and mouse experiments. In contrast to the well established role of some nuclear SDH genes, a functional impact of the mitochondrial genome itself (mtDNA) in cancer development remains unclear. Nevertheless, the extremely high frequency of mtDNA mutations in solid tumors raises the question, whether this small circular genome might be applicable to early cancer detection. This is a meaningful approach, especially in cancers, which tend to spread tumor cells early into bodily fluids or faeces, which can be screened by non-invasive methods. |
format | Text |
id | pubmed-2709939 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Bentham Science Publishers Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-27099392009-12-01 Mitochondrial and Nuclear Genes of Mitochondrial Components in Cancer Kirches, E Curr Genomics Article Although the observation of aerobic glycolysis of tumor cells by Otto v. Warburg had demonstrated abnormalities of mitochondrial energy metabolism in cancer decades ago, there was no clear evidence for a functional role of mutant mitochondrial proteins in cancer development until the early years of the 21(st) century. In the year 2000, a major breakthrough was achieved by the observation, that several genes coding for subunits of the respiratory chain (ETC) complex II, succinate dehydrogenase (SDH) are tumor suppressor genes in heritable paragangliomas, fulfilling Knudson’s classical two-hit hypothesis. A functional inactivation of both alleles by germline mutations and chromosomal losses in the tumor tissue was found in the patients. Later, SDH mutations were also identified in sporadic paragangliomas and pheochromocytomas. Genes of the mitochondrial ATP-synthase and of mitochondrial iron homeostasis have been implicated in cancer development at the level of cell culture and mouse experiments. In contrast to the well established role of some nuclear SDH genes, a functional impact of the mitochondrial genome itself (mtDNA) in cancer development remains unclear. Nevertheless, the extremely high frequency of mtDNA mutations in solid tumors raises the question, whether this small circular genome might be applicable to early cancer detection. This is a meaningful approach, especially in cancers, which tend to spread tumor cells early into bodily fluids or faeces, which can be screened by non-invasive methods. Bentham Science Publishers Ltd. 2009-06 /pmc/articles/PMC2709939/ /pubmed/19949549 http://dx.doi.org/10.2174/138920209788488517 Text en ©2009 Bentham Science Publishers Ltd. http://creativecommons.org/licenses/by/2.5/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Article Kirches, E Mitochondrial and Nuclear Genes of Mitochondrial Components in Cancer |
title | Mitochondrial and Nuclear Genes of Mitochondrial Components in Cancer |
title_full | Mitochondrial and Nuclear Genes of Mitochondrial Components in Cancer |
title_fullStr | Mitochondrial and Nuclear Genes of Mitochondrial Components in Cancer |
title_full_unstemmed | Mitochondrial and Nuclear Genes of Mitochondrial Components in Cancer |
title_short | Mitochondrial and Nuclear Genes of Mitochondrial Components in Cancer |
title_sort | mitochondrial and nuclear genes of mitochondrial components in cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2709939/ https://www.ncbi.nlm.nih.gov/pubmed/19949549 http://dx.doi.org/10.2174/138920209788488517 |
work_keys_str_mv | AT kirchese mitochondrialandnucleargenesofmitochondrialcomponentsincancer |