Nanobiopsy investigation of the subcellular mtDNA heteroplasmy in human tissues

TL;DR

This paper introduces a new method to study mitochondrial DNA mutations at the subcellular level in human tissues, improving understanding of mitochondrial diseases.

Contribution

The novel use of nanobiopsy for subcellular mtDNA analysis in human tissues.

Findings

Nanobiopsy enables subcellular sampling of mtDNA in human tissues.

Next-generation sequencing reveals subcellular mtDNA mutation loads in diseased tissues.

The method improves understanding of clonal expansion of mtDNA variants in mitochondrial diseases.

Abstract

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.

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