Nanobiopsy investigation of the subcellular mtDNA heteroplasmy in human tissues

Mitochondrial function is critical to continued cellular vitality and is an important contributor to a growing number of human diseases. Mitochondrial dysfunction is typically heterogeneous, mediated through the clonal expansion of mitochondrial DNA (mtDNA) variants in a subset of cells in a given t...

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Bibliographic Details
Published in:Scientific reports 2024-06, Vol.14 (1), p.13789-12
Main Authors: Bury, Alexander, Pyle, Angela, Vincent, Amy E., Actis, Paolo, Hudson, Gavin
Format: Article
Language:English
Subjects:
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631/337
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Antibodies
Disease
DNA, Mitochondrial - genetics
Genetic disorders
Heteroplasmy
Heteroplasmy - genetics
High-Throughput Nucleotide Sequencing - methods
Humanities and Social Sciences
Humans
Investigations
Microscopy
Mitochondria
Mitochondria - genetics
Mitochondria - metabolism
Mitochondria - pathology
Mitochondrial Diseases - genetics
Mitochondrial Diseases - metabolism
Mitochondrial Diseases - pathology
Mitochondrial DNA
multidisciplinary
Musculoskeletal system
Mutation
Next-generation sequencing
Research ethics
Science
Science (multidisciplinary)
Tissues
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Summary:Mitochondrial function is critical to continued cellular vitality and is an important contributor to a growing number of human diseases. Mitochondrial dysfunction is typically heterogeneous, mediated through the clonal expansion of mitochondrial DNA (mtDNA) variants in a subset of cells in a given tissue. To date, our understanding of the dynamics of clonal expansion of mtDNA variants has been technically limited to the single cell-level. Here, we report the use of nanobiopsy for subcellular sampling from human tissues, combined with next-generation sequencing to assess subcellular mtDNA mutation load in human tissue from mitochondrial disease patients. The ability to map mitochondrial mutation loads within individual cells of diseased tissue samples will further our understanding of mitochondrial genetic diseases.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-024-64455-0