Eide 2014 Abstract MiP2014
|Reversible mitochondrial DNA mutagenesis.|
Mitochondrial mutations can result in mitochondrial dysfunction, depending on the fraction of mutated molecules as well as the type of the mutation. We have established high-resolution techniques to quantify mutation frequency in mitochondrial DNA (mtDNA) and to measure errors in mitochondrial RNA (mtRNA). Comparing mtDNA mutation frequency with mtRNA integrity allows us to estimate the tolerance level for mtDNA mutation frequency. The mtDNA mutation frequency in embryonic stem (ES) cells is higher than in the aged brain, indicating that mutated mtDNA molecules are deselected during development. mtRNA polymerase introduces errors at a frequency that exceeds the high mutation frequency in ES mtDNA, thereby providing an explanation for the apparent high tolerance for ES mtDNA mutations. In order to characterize the dynamics in mtDNA mutagenesis further, we evaluate mtDNA mutagenesis during induced pluripotent stem (iPS) cell reprogramming and subsequent re-differentiation. Our results show that iPS cell reprogramming induces mutated mtDNA molecules, which are subsequently removed upon re-differentiation. We are currently investigating the role of mtDNA repair in this reversible mtDNA mutagenesis.
• O2k-Network Lab: NO Oslo Eide L
Labels: MiParea: mtDNA;mt-genetics Pathology: Aging;senescence
Organism: Human Tissue;cell: Nervous system, Stem cells
Event: A1, Oral MiP2014
1-Dep Medical Biochem; 2-Dep Microbiol; Oslo Univ Hospital, Univ Oslo, Norway; 3-Dep Clinical Molec Biol Lab Sc (EpiGen), Div Medicine, Akershus Univ Hospital and Univ Oslo, Lørenskog, Norway; 4-Max Planck Inst Biology of Ageing, Cologne, Germany. - [email protected]