Cristae-dependent quality control of the mitochondrial genome

Mitochondrial genomes (mtDNA) encode essential subunits of the mitochondrial respiratory chain. Mutations in mtDNA can cause a shortage in cellular energy supply, which can lead to numerous mitochondrial diseases. How cells secure mtDNA integrity over generations has remained unanswered. Here, we show that the single-celled yeast Saccharomyces cerevisiae can intracellularly distinguish between functional and defective mtDNA and promote generation of daughter cells with increasingly healthy mtDNA content. Purifying selection for functional mtDNA occurs in a continuous mitochondrial network and does not require mitochondrial fission but necessitates stable mitochondrial subdomains that depend on intact cristae morphology. Our findings support a model in which cristae-dependent proximity between mtDNA and the proteins it encodes creates a spatial sphere of influence, which links a lack of functional fitness to clearance of defective mtDNA.

Automated summary

The study shows that yeast can distinguish between functional and defective mtDNA, promoting the generation of healthier daughter cells. Purifying selection for functional mtDNA occurs in a continuous mitochondrial network, depending on intact cristae morphology.