Predavanje Prof. Jirija Neužila

Vljudno vabljeni na predavanje z naslovom

Horizontal transfer of mitochondria in the context of cancer

Jirí Neužil

Griffith University, Southport, Qld, Avstralija

 

v četrtek, 5. aprila 2018 ob 11. uri v predavalnici B220

 

Tumor cells without mitochondrial DNA (mtDNA) reconstitute oxidative phosphorylation (OXPHOS) by acquiring host mitochondria, but the reasons why functional respiration is crucial for tumorigenesis remain unclear. To address this, we used time-resolved analysis of tumor formation by cells devoid of mtDNA and genetic manipulations of OXPHOS. We show that pyrimidine biosynthesis, supported by respiration-linked dihydroorotate dehydrogenase (DHODH), is required to overcome cell cycle arrest, while mitochondrial ATP generation is dispensable for tumorigenesis. Latent DHODH present in mtDNA-deficient cells becomes fully active with restoration of complex III/IV activity and coenzyme Q redox-cycling after mitochondrial transfer, or by the introduction of an alternative oxidase. Conversely, deletion of DHODH interferes with tumor formation even in cells with fully functional OXPHOS, while disruption of mitochondrial ATP synthase has little or no effect. Our results show for the first time that DHODH-driven pyrimidine biosynthesis is the essential pathway that links respiration to tumorigenesis.

 

Note about the speaker. Prof. Neuzil is head of Molecular Therapy Group, Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic and a professor of Molecular Medicine at Griffith University, Southport, Qld, Australia. He has published some 190 original and review papers, mostly in the field of biomedical research, focusing on cancer biology, in particular, the molecular mechanism of apoptosis regulation and the design of selective anti-cancer drugs since the year 2000. His major achievement is the discovery of analogues of vitamin E as novel and selective anti-cancer drugs and the discovery of the mitochondrial complex II as a new and clinically relevant target for anti-cancer drugs. He has pioneered a novel paradigm of efficient cancer therapy, which is based on a specific modification of anti-cancer agents delivering them to mitochondria.

 

Odsečni seminarji

Kontaktni podatki

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