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DarT-mediated mtDNA damage induces dynamic reorganization and selective segregation of mitochondria

Mitochondria are dynamic organelles that play essential roles in cell growth and survival. Processes of fission and fusion are critical for the distribution, segregation, and maintenance of mitochondria and their genomes (mtDNA). While recent work has revealed the significance of mitochondrial organ...

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Autores principales: Dua, Nitish, Seshadri, Akshaya, Badrinarayanan, Anjana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9463037/
https://www.ncbi.nlm.nih.gov/pubmed/36074064
http://dx.doi.org/10.1083/jcb.202205104
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author Dua, Nitish
Seshadri, Akshaya
Badrinarayanan, Anjana
author_facet Dua, Nitish
Seshadri, Akshaya
Badrinarayanan, Anjana
author_sort Dua, Nitish
collection PubMed
description Mitochondria are dynamic organelles that play essential roles in cell growth and survival. Processes of fission and fusion are critical for the distribution, segregation, and maintenance of mitochondria and their genomes (mtDNA). While recent work has revealed the significance of mitochondrial organization for mtDNA maintenance, the impact of mtDNA perturbations on mitochondrial dynamics remains less understood. Here, we develop a tool to induce mitochondria-specific DNA damage using a mitochondrial-targeted base modifying bacterial toxin, DarT. Following damage, we observe dynamic reorganization of mitochondrial networks, likely driven by mitochondrial dysfunction. Changes in the organization are associated with the loss of mtDNA, independent of mitophagy. Unexpectedly, perturbation to exonuclease function of mtDNA replicative polymerase, Mip1, results in rapid loss of mtDNA. Our data suggest that, under damage, partitioning of defective mtDNA and organelle are de-coupled, with emphasis on mitochondrial segregation independent of its DNA. Together, our work underscores the importance of genome maintenance on mitochondrial function, which can act as a modulator of organelle organization and segregation.
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spelling pubmed-94630372023-03-08 DarT-mediated mtDNA damage induces dynamic reorganization and selective segregation of mitochondria Dua, Nitish Seshadri, Akshaya Badrinarayanan, Anjana J Cell Biol Tools Mitochondria are dynamic organelles that play essential roles in cell growth and survival. Processes of fission and fusion are critical for the distribution, segregation, and maintenance of mitochondria and their genomes (mtDNA). While recent work has revealed the significance of mitochondrial organization for mtDNA maintenance, the impact of mtDNA perturbations on mitochondrial dynamics remains less understood. Here, we develop a tool to induce mitochondria-specific DNA damage using a mitochondrial-targeted base modifying bacterial toxin, DarT. Following damage, we observe dynamic reorganization of mitochondrial networks, likely driven by mitochondrial dysfunction. Changes in the organization are associated with the loss of mtDNA, independent of mitophagy. Unexpectedly, perturbation to exonuclease function of mtDNA replicative polymerase, Mip1, results in rapid loss of mtDNA. Our data suggest that, under damage, partitioning of defective mtDNA and organelle are de-coupled, with emphasis on mitochondrial segregation independent of its DNA. Together, our work underscores the importance of genome maintenance on mitochondrial function, which can act as a modulator of organelle organization and segregation. Rockefeller University Press 2022-09-08 /pmc/articles/PMC9463037/ /pubmed/36074064 http://dx.doi.org/10.1083/jcb.202205104 Text en © 2022 Dua et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Tools
Dua, Nitish
Seshadri, Akshaya
Badrinarayanan, Anjana
DarT-mediated mtDNA damage induces dynamic reorganization and selective segregation of mitochondria
title DarT-mediated mtDNA damage induces dynamic reorganization and selective segregation of mitochondria
title_full DarT-mediated mtDNA damage induces dynamic reorganization and selective segregation of mitochondria
title_fullStr DarT-mediated mtDNA damage induces dynamic reorganization and selective segregation of mitochondria
title_full_unstemmed DarT-mediated mtDNA damage induces dynamic reorganization and selective segregation of mitochondria
title_short DarT-mediated mtDNA damage induces dynamic reorganization and selective segregation of mitochondria
title_sort dart-mediated mtdna damage induces dynamic reorganization and selective segregation of mitochondria
topic Tools
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9463037/
https://www.ncbi.nlm.nih.gov/pubmed/36074064
http://dx.doi.org/10.1083/jcb.202205104
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