Salk Institute researchers unveiled a scalable stem-cell platform to generate mitochondrial DNA mutant mice, addressing a key bottleneck in modeling the full diversity of inherited mitochondrial mutations. Led by Ronald Evans, the team developed an embryonic stem cell–based approach that supported creation of a library of 155 mitochondrial DNA mutant cell lines and enabled generation of mitochondrial DNA mutant mice. The work, published in PNAS, links mtDNA variation to mouse development and provides a foundation for studying physiology, adaptation, and disease mechanisms. Evans highlighted that more than 260 inherited mtDNA disease mutations have been identified in humans, but limited models have constrained mechanistic insight and therapeutic development. The platform is designed to accelerate genetically precise mitochondrial disorder research and downstream therapeutic innovation.