Decreasing mitochondrial RNA polymerase activity reverses biased inheritance of hypersuppressive mtDNA
Name
journal.pgen.1009808.pdf
Description
Published version
Size
2.04 MB
Format
Adobe PDF
Checksum (MD5)
e37b0ce4ca9fe3fe1b8ae904391f6210
Author(s)
Corbi, Daniel
Amon, Angelika
Date Issued
October 2021
Journal
PLOS Genetics
Publisher
Public Library of Science (PLoS)
Citation
Corbi, Daniel and Amon, Angelika. 2021. "Decreasing mitochondrial RNA polymerase activity reverses biased inheritance of hypersuppressive mtDNA." PLOS Genetics, 17 (10).
Version
Final published version
Abstract
Faithful inheritance of mitochondrial DNA (mtDNA) is crucial for cellular respiration/oxidative phosphorylation and mitochondrial membrane potential. However, how mtDNA is transmitted to progeny is not fully understood. We utilized hypersuppressive mtDNA, a class of respiratory deficient Saccharomyces cerevisiae mtDNA that is preferentially inherited over wild-type mtDNA (rho+), to uncover the factors governing mtDNA inheritance. We found that some regions of rho+ mtDNA persisted while others were lost after a specific hypersuppressive takeover indicating that hypersuppressive preferential inheritance may partially be due to active destruction of rho+ mtDNA. From a multicopy suppression screen, we found that overexpression of putative mitochondrial RNA exonuclease PET127 reduced biased inheritance of a subset of hypersuppressive genomes. This suppression required PET127 binding to the mitochondrial RNA polymerase RPO41 but not PET127 exonuclease activity. A temperature-sensitive allele of RPO41 improved rho+ mtDNA inheritance over a specific hypersuppressive mtDNA at semi-permissive temperatures revealing a previously unknown role for rho+ transcription in promoting hypersuppressive mtDNA inheritance.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biology
Howard Hughes Medical Institute
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1371/journal.pgen.1009808
