Decreasing mitochondrial RNA polymerase activity reverses biased inheritance of hypersuppressive mtDNA

Area of Science:

• Mitochondrial genetics
• Yeast molecular biology
• Cellular respiration

Background:

• Faithful mitochondrial DNA (mtDNA) inheritance is essential for cellular respiration and maintaining mitochondrial membrane potential.
• The precise mechanisms governing mtDNA transmission to progeny remain incompletely understood.
• Hypersuppressive mtDNA in Saccharomyces cerevisiae offers a model to study preferential mtDNA inheritance over wild-type (rho+) mtDNA.

Purpose of the Study:

• To investigate the factors influencing mitochondrial DNA (mtDNA) inheritance patterns.
• To identify genetic elements and pathways that regulate the preferential transmission of hypersuppressive mtDNA over wild-type mtDNA in yeast.

Main Methods:

• Utilized hypersuppressive mtDNA in Saccharomyces cerevisiae to study inheritance dynamics.
• Conducted multicopy suppression screens to identify genetic modifiers of mtDNA inheritance.
• Employed a temperature-sensitive allele of mitochondrial RNA polymerase RPO41 to probe transcription's role.

Main Results:

• Observed partial persistence and loss of wild-type (rho+) mtDNA regions during hypersuppressive takeover, suggesting active rho+ mtDNA destruction.
• Overexpression of PET127, a mitochondrial RNA exonuclease, reduced biased inheritance of certain hypersuppressive genomes, dependent on its binding to RPO41.
• A temperature-sensitive RPO41 allele enhanced rho+ mtDNA inheritance over specific hypersuppressive mtDNA at semi-permissive temperatures.

Conclusions:

• Hypersuppressive mtDNA preferential inheritance may involve active degradation of wild-type mtDNA.
• PET127's interaction with RPO41, independent of its exonuclease activity, modulates mtDNA inheritance bias.
• Wild-type mtDNA transcription plays a previously unrecognized role in promoting hypersuppressive mtDNA inheritance.