Understanding the mitochondrial DNA replication machinery [Nodes Seminar]

Recent evidence directly links mitochondrial metabolism to neurological and neurodegenerative disorders. Mutations in nuclear genes essential for mitochondrial DNA (mtDNA) maintenance lead to severe neurological conditions. Moreover, mtDNA structural defects have also been linked to neurodegenerative disorders and cancer progression. The replication of mtDNA by the mitochondrial DNA replisome is the primary process that ensures mtDNA integrity and is vital for mitochondrial function; however, its mechanism remains largely unexplored. Understanding the mtDNA replication process is crucial for deciphering the pathogenesis of related disorders and for developing treatments. In this talk, I will summarise our efforts to study this system, focusing on recent discoveries regarding the DNA polymerase gamma.