Caloric restriction enhances inheritance of wild-type mitochondrial DNA in Saccharomyces cerevisiae

Area of Science:

• Cell Biology
• Genetics
• Mitochondrial Biology

Background:

• Mitochondrial DNA (mtDNA) in Saccharomyces cerevisiae is typically homoplasmic but prone to mutations.
• Replication via mtDNA recombinase Mhr1p creates tandem concatemers, influencing inheritance.
• Hypersuppressive (HS) ρ⁻ mtDNA with deletions often dominates in crosses due to replicative advantage.

Purpose of the Study:

• To investigate the impact of caloric restriction (CR) on mitochondrial distribution and mtDNA inheritance.
• To understand the mechanism of selective transmission of wild-type (ρ⁺) mtDNA during yeast cell division.

Main Methods:

• Utilized confocal imaging and flow cytometry to analyze mitochondrial distribution and mtDNA content.
• Compared yeast grown under caloric restriction (0.5% glucose) versus glucose-rich conditions.
• Investigated the role of the Mhr1p-dependent mechanism in mtDNA inheritance.

Main Results:

• Caloric restriction induced preselection and transmission of ρ⁺ mtDNA-mitochondria into buds before fusion (ρ⁺ mtDNA-MPT).
• The rate of ρ⁺ progeny significantly increased under CR conditions compared to normal glucose media.
• The Mhr1p-dependent mechanism was crucial for CR-enhanced ρ⁺ mtDNA inheritance.

Conclusions:

• Caloric restriction enhances ρ⁺ mtDNA-mitochondrial preselection and transmission (ρ⁺ mtDNA-MPT) in yeast.
• CR promotes the formation of wild-type mtDNA homoplasmy through an Mhr1p-dependent pathway.
• This study reveals a novel mechanism influencing mtDNA inheritance under nutrient stress.