Mitochondrial DNA maintenance in mammals and beyond


Mitochondrial DNA (mtDNA) encodes essential cellular machinery in humans and almost all eukaryotes. But the mitochondrion is an awkward place to store genetic information safely; it’s a physically and chemically damaging environment involving frequent and error-prone replication. Most genes for mitochondrial machinery have been transferred to the nucleus since endosymbiosis. So why do mitochondria — including ours — retain any genes at all? Why do different species retain dramatically different mitochondrial gene counts? And how do they mitigate against the inevitable damage in these essential genes — which can give rise to devastating human diseases?
Our work combines bioinformatics, modelling, heteroplasmy profiling in mammalian models and across taxa, and microscopy to explore these questions. We aim to test long-standing and new hypotheses about why mtDNA retain genes, how species in different kingdoms and with different lifestyles can use mitochondrial structure and dynamics to segregate mtDNA damage. I’ll ask the audience which topics under this umbrella are of most interest, then depending on response I can either focus on the more human-disease-relevant, mammalian story or the broader picture across species with weird and wonderful mitochondria (teaser: some of these are vital for human health too!)