Experimental evolution improves mitochondrial genome quality control in Saccharomyces cerevisiae and extends its...

Area of Science:

• Cell Biology
• Genetics
• Evolutionary Biology

Background:

• Mitochondria are vital organelles with complex interactions between nuclear and mitochondrial genomes.
• Mitochondrial dysfunction leads to disease, highlighting the need for mechanisms maintaining mitochondrial stability.
• Existing pathways monitor mitochondrial quality, but their potential for enhancement under stress is unclear.

Purpose of the Study:

• To investigate if yeast cells can evolve enhanced mitochondrial DNA (mtDNA) stability under continuous stress.
• To identify molecular mechanisms underlying adaptation to mtDNA damage.
• To explore the physiological consequences of enhanced mtDNA retention.

Main Methods:

• Experimental evolution of yeast cells under ethidium bromide (EtBr) treatment to induce mtDNA damage.
• Selection for efficient respiration and resistance to mtDNA-damaging reagents.
• Genetic analysis to identify mutations in evolved yeast lines.
• Assessment of replicative lifespan in adapted cells.

Main Results:

• Most evolved yeast lines showed improved ability to maintain functional mtDNA when exposed to mtDNA-damaging agents.
• Mutations in the mitochondrial NADH dehydrogenase NDE1 gene were identified in most adapted lines.
• Enhanced mtDNA retention correlated with a prolonged replicative lifespan.
• Other cellular pathways were also implicated in the adaptation process.

Conclusions:

• Yeast can evolve enhanced mitochondrial DNA (mtDNA) stability and function in response to genotoxic stress.
• The NDE1 gene and potentially other pathways play crucial roles in this adaptive response.
• Adaptations for mtDNA maintenance have significant implications for cellular aging and lifespan.