2017
DOI: 10.1016/j.celrep.2017.11.031
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Pervasive within-Mitochondrion Single-Nucleotide Variant Heteroplasmy as Revealed by Single-Mitochondrion Sequencing

Abstract: Summary A number of mitochondrial diseases arise from Single Nucleotide Variant (SNV) accumulation in multiple mitochondria. Here we present a method for identification of variants present at the single mitochondrion level in individual mouse and human neuronal cells allowing for extremely high resolution study of mitochondrial mutation dynamics. We identified extensive heteroplasmy between individual mitochondrion, along with three high confidence variants in mouse and one in human that were present in multip… Show more

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Cited by 57 publications
(97 citation statements)
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References 34 publications
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“…At first, analysis of a single mitochondrion was limited by the technological resolution of mutational detection (Reiner et al, 2010). However, a recent study investigated mtDNA sequence variation within 118 isolated mitochondria from mouse neurons and astrocytes (Morris et al, 2017). Whole mtDNA sequencing of each of the isolated mitochondria revealed an average of 3.9 (± 5.71 SD) single heteroplasmic nucleotide variants (SNVs) in the tested mitochondrial population per nucleotide position.…”
Section: Selection Acts On the Phenotype-the Various Levels Of Mitochmentioning
confidence: 99%
“…At first, analysis of a single mitochondrion was limited by the technological resolution of mutational detection (Reiner et al, 2010). However, a recent study investigated mtDNA sequence variation within 118 isolated mitochondria from mouse neurons and astrocytes (Morris et al, 2017). Whole mtDNA sequencing of each of the isolated mitochondria revealed an average of 3.9 (± 5.71 SD) single heteroplasmic nucleotide variants (SNVs) in the tested mitochondrial population per nucleotide position.…”
Section: Selection Acts On the Phenotype-the Various Levels Of Mitochmentioning
confidence: 99%
“…Future experimental studies quantifying the importance of selective mitophagy under physiological conditions would be beneficial for understanding heteroplasmy variance dynamics. The ubiquity of heteroplasmy (Morris et al, 2017;Payne et al, 2012;Ye et al, 2014) suggests that a neutral drift approach to mitochondrial genetics may be justified, which contrasts with the studies of Tam et al (2013Tam et al ( , 2015 and Mouli et al (2009) which focus purely on the selective effects of mitochondrial networks.…”
Section: Discussionmentioning
confidence: 99%
“…Our basic approach therefore also differs from previous modelling attempts, since our model is neutral with respect to genetics (no replicative advantage or selective mitophagy) and the mitochondrial network (no selective fusion). Evidence for negative selection of particular mtDNA mutations has been observed in vivo (Morris et al, 2017;Ye et al, 2014); we therefore extend our analysis to explore selectivity in the context of mitochondrial quality control using our simplified framework.…”
Section: Introductionmentioning
confidence: 97%
“…Morris et al, in their study on single mitochondrion mtDNA deep sequencing originating from neural tissue in both mouse and human, were able to demonstrate several populations of mtDNA within the same cell. They showed extensive intracellular heteroplasmy with a significant percentage of mtDNA harbouring single nucleotide variance with potentially detrimental effects on mitochondrial function [58].…”
Section: Mitochondrial Dynamics -Fusion and Fissionmentioning
confidence: 99%