Nuclear and mitochondrial genomes are subjected to dynamic modifications that are taken care of by distinct repair mechanisms.
We have found that modifications in the DNA in nucleus and mitochondria serve distinct roles in cellular regulation of metabolism.
Projects
- Metabolism of branched-chain amino acids. Inability to degrade branched-chain amino acids (leucine, isoleucine, valine) underlies pathology in Maple Syrup Urine Disease (MSUD). Toxic metabolites accumulate, but downstream fatty acids; branched-chain fatty acids are also prevented from being formed. The effect of these fatty acids are largely overlooked.
In a collaboration project (PReventADALL), we investigate their importance in protecting against autoimmune disease. Pancreatic Ductal Adenocarcinoma (PDAC) depends heavily on this metabolism. We are developing inhibitors of the BCAT2 transaminase. - Huntington’s disease is a neurodegenerativ disorder with association to mitochondrial dysfunction. We’ve found that progression of disease correlates with DNA integrity in peripheral mononuclear blood cells, and speculate that onset of disease is dictated by individual mitochondrial capacity.
- Adult Macular Degeneration (AMD). We investigate whether mitochondrial aberrations in Retinal Epithelial Pigmental cells cause metabolic changes that underlie AMD.
- Personalized mitochondrial function. Heteroplasmies and cardiolipin oxidation are two separate features that influence mitochondrial capacity. We investigate the contribution to develop more precise prediction of individual mitochondrial function.
Collaboration
- Bjørn Dalhus, University of Oslo
- Goran Petrovski, Centre of Eye Research, University of Oslo and Oslo University Hospital
- Hana Hansikova, 1st Charles University in Prague and General University Hospital in Prague, Czech Republic
- Katja Benedicte Prestø Elgstøen, Oslo University Hospital
- Knut Rudi, Norwegian University of Life Science NMBU
- Karin Lødrup Carlsen, University of Oslo
- Magnar Bjørås, University of Oslo
- Zdenka Ellederova & Jan Motlik, Institute of Animal Physiology and Genetics, Libechov, Czech Republic