Decreasing mitochondrial RNA polymerase activity reverses biased inheritance of hypersuppressive mtDNA.

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 Saccharomyc...

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Main Authors: Daniel Corbi, Angelika Amon
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-10-01
Series:PLoS Genetics
Online Access:https://doi.org/10.1371/journal.pgen.1009808
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author Daniel Corbi
Angelika Amon
author_facet Daniel Corbi
Angelika Amon
author_sort Daniel Corbi
collection DOAJ
description 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.
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spelling doaj.art-f909f2d7178f451eac63b3dc87e1101b2022-12-21T22:42:15ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042021-10-011710e100980810.1371/journal.pgen.1009808Decreasing mitochondrial RNA polymerase activity reverses biased inheritance of hypersuppressive mtDNA.Daniel CorbiAngelika AmonFaithful 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.https://doi.org/10.1371/journal.pgen.1009808
spellingShingle Daniel Corbi
Angelika Amon
Decreasing mitochondrial RNA polymerase activity reverses biased inheritance of hypersuppressive mtDNA.
PLoS Genetics
title Decreasing mitochondrial RNA polymerase activity reverses biased inheritance of hypersuppressive mtDNA.
title_full Decreasing mitochondrial RNA polymerase activity reverses biased inheritance of hypersuppressive mtDNA.
title_fullStr Decreasing mitochondrial RNA polymerase activity reverses biased inheritance of hypersuppressive mtDNA.
title_full_unstemmed Decreasing mitochondrial RNA polymerase activity reverses biased inheritance of hypersuppressive mtDNA.
title_short Decreasing mitochondrial RNA polymerase activity reverses biased inheritance of hypersuppressive mtDNA.
title_sort decreasing mitochondrial rna polymerase activity reverses biased inheritance of hypersuppressive mtdna
url https://doi.org/10.1371/journal.pgen.1009808
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