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2014 | 61 | 4 | 671-678
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Role of mitochondria in carcinogenesis

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Mitochondria play the central role in supplying cells with ATP and are also the major source of reactive oxygen species (ROS) - molecules of both regulatory and destructive nature. Dysfunction of mitochondrial metabolism and/or morphology have been frequently reported in human cancers. This dysfunction can be associated with mitochondrial DNA (mtDNA) damage, which may be changed into mutations in mtDNA coding sequences, or the displacement-loop region, changes in the mtDNA copy number or mtDNA microsatellite instability. All these features are frequently associated with human cancers. Mutations in mtDNA can disturb the functioning of the ROS-producing organelle and further affect the entire cell which may contribute to genomic instability typical for cancer cells. Although the association between some mtDNA mutations and cancer is well established, the causative relationship between these two features is largely unknown. A hint suggesting the driving role of mtDNA mutations in carcinogenesis comes from the observation of tumor promotion after mtDNA depletion. Mitochondria with damaged DNA may alter signaling of the mitochondrial apoptosis pathway promoting cancer cell survival and conferring resistance to anticancer drugs. This resistance may be underlined by mtDNA copy number depletion. Therefore, mitochondria are considered a promising target in anticancer therapy and several mitochondria-targeting drugs are in preclinical and clinical trials. Some other aspects of mitochondrial structure and functions, including morphology and redox potential, can also be associated with cancer transformation and constitute new anticancer targets. Recently, several studies have disclosed new mechanisms underlying the association between mitochondria and cancer, including the protection of mtDNA by telomerase, suggesting new approaches in mitochondria-oriented anti-cancer therapy.
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  • Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Łódź, Poland
  • Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Łódź, Poland
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