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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2022
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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. |
format | Online Article Text |
id | pubmed-9463037 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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