QBI Neuroscience Seminar: 'The role of mitochondrial dysfunction in neurodegenerative diseases'
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- Professor Aleksandra Filipovska, Laboratory Head, Mitochondrial Medicine and Biology
Harry Perkins Institute of Medical Research, Perth, WA
Title: “The role of mitochondrial dysfunction in neurodegenerative diseases'
Abstract:
The size and organization of the animal mitochondrial genome has been reduced and compacted significantly since its endosymbiosis from an α-proteobacterial ancestor. This compaction has necessitated the evolution of unique mechanisms to facilitate rapid changes in gene expression in response to the changing energy demands of the cell. The mitochondrial transcriptome encodes proteins that are subunits of the respiratory chain, responsible for most of the energy production required by cells. Consequently the coordinated regulation of the mitochondrial transcriptome by the nucleus is of particular importance for the maintenance of cell health and energy metabolism, particularly in high energy demand organs such as the brain and heart. We have been investigating the unusual features of mitochondrial RNAs and the RNA-binding proteins that control their production, maturation, translation and stabilization to understand the regulation of mitochondrial gene expression and its contribution to health and disease. I will highlight the devastating consequences of dysregulated mitochondrial gene expression in different models of disease in mice and humans caused by genetic disruption of RNA-binding proteins. Mouse models of disease have enabled us to understand the in vivo role of fundamental processes that regulate mitochondrial RNA metabolism and the pathogenesis of diseases caused by impaired gene expression that cause neurodegeneration.
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