A new automated tool to quantify nucleoid distribution within mitochondrial networks

Abstract Mitochondrial DNA (mtDNA) maintenance is essential to sustain a functionally healthy population of mitochondria within cells. Proper mtDNA replication and distribution within mitochondrial networks are essential to maintain mitochondrial homeostasis. However, the fundamental basis of mtDNA...

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Autores principales:	Hema Saranya Ilamathi, Mathieu Ouellet, Rasha Sabouny, Justine Desrochers-Goyette, Matthew A. Lines, Gerald Pfeffer, Timothy E. Shutt, Marc Germain
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0eca7eaf2ac94324bd6e7a0fe98724dc
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spelling	oai:doaj.org-article:0eca7eaf2ac94324bd6e7a0fe98724dc2021-11-28T12:16:25ZA new automated tool to quantify nucleoid distribution within mitochondrial networks10.1038/s41598-021-01987-92045-2322https://doaj.org/article/0eca7eaf2ac94324bd6e7a0fe98724dc2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01987-9https://doaj.org/toc/2045-2322Abstract Mitochondrial DNA (mtDNA) maintenance is essential to sustain a functionally healthy population of mitochondria within cells. Proper mtDNA replication and distribution within mitochondrial networks are essential to maintain mitochondrial homeostasis. However, the fundamental basis of mtDNA segregation and distribution within mitochondrial networks is still unclear. To address these questions, we developed an algorithm, Mitomate tracker to unravel the global distribution of nucleoids within mitochondria. Using this tool, we decipher the semi-regular spacing of nucleoids across mitochondrial networks. Furthermore, we show that mitochondrial fission actively regulates mtDNA distribution by controlling the distribution of nucleoids within mitochondrial networks. Specifically, we found that primary cells bearing disease-associated mutations in the fission proteins DRP1 and MYH14 show altered nucleoid distribution, and acute enrichment of enlarged nucleoids near the nucleus. Further analysis suggests that the altered nucleoid distribution observed in the fission mutants is the result of both changes in network structure and nucleoid density. Thus, our study provides novel insights into the role of mitochondria fission in nucleoid distribution and the understanding of diseases caused by fission defects.Hema Saranya IlamathiMathieu OuelletRasha SabounyJustine Desrochers-GoyetteMatthew A. LinesGerald PfefferTimothy E. ShuttMarc GermainNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hema Saranya Ilamathi Mathieu Ouellet Rasha Sabouny Justine Desrochers-Goyette Matthew A. Lines Gerald Pfeffer Timothy E. Shutt Marc Germain A new automated tool to quantify nucleoid distribution within mitochondrial networks
description	Abstract Mitochondrial DNA (mtDNA) maintenance is essential to sustain a functionally healthy population of mitochondria within cells. Proper mtDNA replication and distribution within mitochondrial networks are essential to maintain mitochondrial homeostasis. However, the fundamental basis of mtDNA segregation and distribution within mitochondrial networks is still unclear. To address these questions, we developed an algorithm, Mitomate tracker to unravel the global distribution of nucleoids within mitochondria. Using this tool, we decipher the semi-regular spacing of nucleoids across mitochondrial networks. Furthermore, we show that mitochondrial fission actively regulates mtDNA distribution by controlling the distribution of nucleoids within mitochondrial networks. Specifically, we found that primary cells bearing disease-associated mutations in the fission proteins DRP1 and MYH14 show altered nucleoid distribution, and acute enrichment of enlarged nucleoids near the nucleus. Further analysis suggests that the altered nucleoid distribution observed in the fission mutants is the result of both changes in network structure and nucleoid density. Thus, our study provides novel insights into the role of mitochondria fission in nucleoid distribution and the understanding of diseases caused by fission defects.
format	article
author	Hema Saranya Ilamathi Mathieu Ouellet Rasha Sabouny Justine Desrochers-Goyette Matthew A. Lines Gerald Pfeffer Timothy E. Shutt Marc Germain
author_facet	Hema Saranya Ilamathi Mathieu Ouellet Rasha Sabouny Justine Desrochers-Goyette Matthew A. Lines Gerald Pfeffer Timothy E. Shutt Marc Germain
author_sort	Hema Saranya Ilamathi
title	A new automated tool to quantify nucleoid distribution within mitochondrial networks
title_short	A new automated tool to quantify nucleoid distribution within mitochondrial networks
title_full	A new automated tool to quantify nucleoid distribution within mitochondrial networks
title_fullStr	A new automated tool to quantify nucleoid distribution within mitochondrial networks
title_full_unstemmed	A new automated tool to quantify nucleoid distribution within mitochondrial networks
title_sort	new automated tool to quantify nucleoid distribution within mitochondrial networks
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0eca7eaf2ac94324bd6e7a0fe98724dc
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A new automated tool to quantify nucleoid distribution within mitochondrial networks

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