Mitochondrial medicine: a long journey through the magic circle and beyond
The 2015/16 Annual lecture of the Department of Molecular Medicine will be given by Massimo Zeviani of the MRC Mitochondrial Biology Unit and University of Cambridge, UK on the 29th of April 2016 at 5.30 pm at Collegio A Volta (17 via A Ferrata, Pavia). The lecture is entitled Mitochondrial medicine: a long journey through the magic circle and beyond and the poster of the lecture can be found here. All members of the Department and other members of the academic community in Pavia, students and staff, are welcome to attend. The abstract of the lecture and a short biographical sketch are enclosed below, as supplied by the speaker.
Abstract. Mitochondria are the major source of ATP that is synthesized by the respiratory chain through the process of oxidative phosphorylation (OXPHOS), a complex biochemical process carried out through the dual control of physically separated, but functionally interrelated, genomes, nuclear and mitochondrial DNAs. The genetic and biochemical intricacy of mitochondrial bioenergetics explains the extreme heterogeneity of mitochondrial disorders, a group of highly invalidating human conditions, for which no effective treatment is nowadays available. In addition to bioenergetic failure, other mechanisms are probably predominant in the pathogenesis of specific syndromes, such as alterations of cellular redox status, the production of reactive oxygen species, compromised Ca2+ homeostasis, mitochondrial protein and organelle quality control, and mitochondrial pathways of apoptosis. By investigating selected families and patients, we have identified several new disease genes, each responsible of distinct defects in the respiratory chain, mtDNA metabolism, or both, associated with paediatric or adult-onset clinical presentations. I will focus this lecture on an expanding group of disorders characterized by mtDNA instability, either sporadically occurring in critical tissues (e.g. muscle and brain) or caused by mutations in a number of different nucleus encoded genes that directly control mtDNA maintenance and replication, or are involved in the mitochondrial quality control system.
Biography. Massimo Zeviani graduated cum laude in Medicine at the University of Padua. He specialised in Endocrinology and Neurology, and obtained a PhD in Genetics at the University René Descartes in Paris. In 1984, he moved to Columbia University, New York, where he worked as a post-doc for five years with Billi Di Mauro on the biochemical and molecular definition of respiratory chain disorders. In 1990, he became Assistant and then Associate in Neurology at the Department of Biochemistry and Genetics of the Istituto Neurologico “C. Besta” in Milan where he organized a laboratory of molecular biology on mitochondrial disorders. In 2001 he became the director of the Unit of Molecular Neurogenetics and, in 2011 he became the director of the Department of Molecular Medicine of the same Institute. In January 2013, he was appointed Director of the MRC Mitochondrial Biology Unit in Cambridge, UK. In June 2013, he was awarded the Grand Prix of the NRJ Foundation, Paris, for “Genetics of degenerative diseases”. Author of ≈300 scientific publications in peer-reviewed journals (H index 70), he has identified and characterized numerous disease genes associated with OXPHOS defects, contributing to the elucidation of the molecular pathogenesis of mitochondrial disorders. More recently he focused on the development of therapeutic approaches to treat these conditions in experimental models and, eventually, patients.
Figure. Projection map at 5 Å resolution of the yeast ADP/ATP carrier with the specific inhibitor atractyloside bound. Courtesy of Edmund Kunji, MRC Mitochondrial Biology Unit, Cambridge