1. Cristae-dependent quality control of the mitochondrial genome
- Author
-
Jakubke, Christopher, Roussou, Rodaria, Maiser, Andreas, Schug, Christina, Thoma, Felix, Bunk, David, Hörl, David, Leonhardt, Heinrich, Walter, Peter, Klecker, Till, and Osman, Christof
- Subjects
Biochemistry and Cell Biology ,Genetics ,Biological Sciences ,Underpinning research ,1.1 Normal biological development and functioning ,Generic health relevance - Abstract
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.
- Published
- 2021