Partial inhibition of mitochondrial-linked pyrimidine synthesis increases tumorigenic potential and lysosome accumulation
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The correlation between mitochondrial function and oncogenesis is complex and is not fully understood. Here we determine the importance of mitochondrial-linked pyrimidine synthesis for the aggressiveness of cancer cells. The enzyme dihydroorotate dehydrogenase (DHODH) links oxidative phosphorylation to de novo synthesis of pyrimidines. We demonstrate that an inhibition of DHODH results in a respiration-independent significant increase of anchorage-independent growth but does not affect DNA repair ability. Instead, we show an autophagy-independent increase of lysosomes. The results of this study suggest that inhibition of mitochondrial-linked pyrimidine synthesis in cancer cells results in a more aggressive tumor phenotype.
Originalsprog | Engelsk |
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Tidsskrift | Mitochondrion |
Vol/bind | 64 |
Sider (fra-til) | 73-81 |
Antal sider | 9 |
ISSN | 1567-7249 |
DOI | |
Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
This research was funded by the Nordea-fonden, Olav Thon Foundation, Sven Wewers fond, Novo Nordisk Foundation (NNF17OC0027812), Danish Cancer Support; Bjarne Jensens Fond; AP Møller Fonden. L.R. is a member of the Clinical Academic Group: Recovery Capacity After Acute Illness in An Aging Population (RECAP).
Publisher Copyright:
© 2022
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