BBB Seminar: Laurence Bindoff
Studying mitochondrial disease mechanisms
Department of Clinical Medicine, University of Bergen
The mitochondrial respiratory chain (MRC) links the oxidation of metabolic fuels to the phosphorylation of ADP and is the final common pathway for cellular energy metabolism. While the majority of proteins that make up the five multisubunit complexes of this pathway are encoded by chromosomal genes, 13 proteins are encoded on a genome found within the mitochondria themselves, mitochondrial DNA (mtDNA), a 16.5 kb circular genome inherited only from the mother. Defects of the mitochondrial respiratory chain are well recognised causes of disease and disability. They are associated with a variety of phenotypes including muscle disease (myopathy), disorders affecting eye movement (progressive external ophthalmoplegia - PEO), blindness, brain disease (encephalopathy) and rapidly fatal disorders of brain metabolism occurring at or shortly after birth. These disorders are not rare; recent studies in England and Sweden show a minimum prevalence of ca. 1:8000.
In order to understand more about the cellular consequences and disease mechanisms involved, we have established disease models of different types of mitochondrial disease. This talk will focus on three ongoing areas of research; studies of the mitochondrial DNA polymerase, polymerase gamma; studies of the intramitochondrial iron-sulphur scaffold protein, ISCU, and studies of ELAC2 and its role in mitochondrial transcript processing.
Host: Jan Haavik, Department of Biomedicine