A new platform for studying mitochondrial DNA mutations implicated in human disease could revolutionize research in health, disease and evolution, and accelerate efforts to develop treatments for mitochondrial disorders. Salk Institute (CA, USA) researchers have developed a scalable embryonic stem cell-based platform for more efficient production of mitochondrial DNA (mtDNA) mutant mice, paving the way for therapeutic development, as well as research investigating the role of mtDNA in physiology, adaptation and disease mechanisms. Already, the technology has been used to generate a library of 155 mtDNA mutant cell lines and reveal links between mouse development and mitochondrial function that could herald new treatments for mitochondrial disorders and perhaps other conditions like cancer or aging. Famed in science class as ‘the powerhouse of the cell’, mitochondria are central to energy metabolism and cellular signaling. Mutations in mtDNA, therefore, can be incredibly disruptive to these processes and may contribute to human disease. To date, more than 260 pathogenic germline mtDNA mutations have been identified in humans, leading to diverse and often tissue-specific disorders. Moreover, population-specific mtDNA variants arise through evolution and may influence adaptation and disease susceptibility. To fully understand the impact of this variation, researchers require animal models that represent the diversity of human mtDNA mutations, but these are unfortunately lacking. Despite recent base-editing approaches that enable direct mtDNA modification, this roadblock continues to limit mechanistic insight and therapeutic development. With their stem cell-based platform, the researchers behind the new study are hoping to change that. They performed random mutagenesis using…
