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Horizontal transfer of mitochondria and its role in carcinogenesis
Nováková, Anna ; Neužil, Jiří (advisor) ; Rösel, Daniel (referee)
Mitochondria are essential organelles as they produce most ATP to support cellular activities, synthesize critical metabolic factors and are involved in lipid and phospholipid metabolism as well as calcium signalling. The oxidative phosphorylation (OXPHOS) system, present at the inner mitochondrial membrane, plays role in regulation of cellular metabolism and survival of cancer cells. Recent studies show importance of OXPHOS in growth of cancer cells via regulation of the de novo pyrimidine synthesis pathway. Dihydroorotate dehydrogenase (DHODH), a flavoprotein localized in the inner mitochondrial membrane, converts dihydroorotate (DHO) to orotate within the de novo pyrimidine synthesis pathway, generating electrons that are transferred, via redox- cycling of ubiquinone, to complex III (CIII) of respiratory chain. Since DHODH is functionally linked to CIII activity, impairment of respiration results in reduced activity of DHODH and pyrimidine synthesis. Therefore, mitochondrial damage or mutation in mitochondrial DNA (mtDNA) leads to decreased respiration, cancer cell proliferation and delay of tumour growth. As a compensation for damaged mitochondria, horizontal transfer of functional mitochondria from donor somatic cells to the mitochondria-damaged tumour cells was demonstrated. This...
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