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Jakubke, Christopher; Roussou, Rodaria; Maiser, Andreas; Schug, Christina; Thoma, Felix; Bunk, David; Horl, David; Leonhardt, Heinrich; Walter, Peter; Klecker, Till und Osman, Christof (2021): Cristae-dependent quality control of the mitochondrial genome. In: Science Advances, Bd. 7, Nr. 36, eabi8886

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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.

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