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The NO-Age and NO-AD Seminar Series 18 ‘Mitochondrial genome mosaicism and resistance to damage’ by Dr. Steven Zuryn Queensland Brain Institute, The University of Queensland, Australia
Speaker: Steven Zuryn

Title: Mitochondrial genome mosaicism and resistance to damage

Mitochondria contain multiple copies of their own genome (mtDNAs) that encode proteins important for energy generation. Mutations in mtDNAs cause severe metabolic diseases that are heritable. These mutations can also accumulate as we age. We have studied the distribution of mtDNAs in C. elegans cells, finding that mutations evolve in stereotyped mosaic patterns between different tissues. This distribution is determined by the activity of a quality control pathway called mitochondrial autophagy (mitophagy), driven by the PINK1-parkin signalling axis. PINK1 and parkin genes are mutated in early-onset Parkinson’s disease implying links between mtDNA mutations and neurodegeneration. Indeed, we find that mutations in PINK1/parkin enhance mtDNA mutation levels in neurons and that proteotoxic species associated with Alzheimer’s and Huntington’s diseases can inhibit mitophagy resulting in increased mtDNA mutation levels in the nervous system. Counteracting the effect of mtDNA mutations, we discovered a new role for the conserved factor ATFS-1/Atf5, which when localised to mitochondria, promotes the repair of mtDNAs and shields cellular function from targeted and age-associated mtDNA damage.

Steven Zuryn obtained his PhD at the University of Queensland, studying mitochondrial physiology. He then pursued postdoctoral research at the Institut Génétique Biologie Moléculaire Cellulaire (IGBMC) in Strasbourg, France, where he worked on epigenetic mechanisms that ensure the robustness of changes in cell identity. In late 2015, Steven opened his own laboratory at the Queensland Brain Institute, University of Queensland. His lab works on mitochondrial biology and epigenetics to uncover fundamental genetic principles of the mitochondrial genome (mtDNA). Throughout his research career, Steven has capitalised on the powerful genetic model system of C. elegans to address comple

Jun 7, 2021 02:00 PM in Oslo

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