A new automated tool to quantify nucleoid distribution within mitochondrial networks

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 segregati...

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Bibliographic Details
Published in:Scientific reports 2021-11, Vol.11 (1), p.22755-14, Article 22755
Main Authors: Ilamathi, Hema Saranya, Ouellet, Mathieu, Sabouny, Rasha, Desrochers-Goyette, Justine, Lines, Matthew A., Pfeffer, Gerald, Shutt, Timothy E., Germain, Marc
Format: Article
Language:English
Subjects:
631/80/2373
631/80/642/333
Cell Nucleus - genetics
Cell Nucleus - metabolism
DNA Replication
DNA, Mitochondrial - genetics
DNA, Mitochondrial - metabolism
Dynamins - genetics
Dynamins - metabolism
Homeostasis
Humanities and Social Sciences
Humans
Medicin och hälsovetenskap
Mitochondria
Mitochondria - genetics
Mitochondria - metabolism
Mitochondrial DNA
Mitochondrial Dynamics
multidisciplinary
Myosin Heavy Chains - genetics
Myosin Heavy Chains - metabolism
Myosin Type II - genetics
Myosin Type II - metabolism
Nucleoids
Science
Science (multidisciplinary)
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-01987-9