Evidence map›Paper›PMID 42127801›Full record

ArticleDevelopmental cell2026

Single-molecule mitochondrial DNA imaging reveals heteroplasmy dynamics shaped by developmental bottlenecks and selection in vivo.

Rajini Chandrasegaram, Sara Gottardo, Abhilesh Dhawanjewar, Antony M Hynes-Allen, Beitong Gao, Suvagata Roy Chowdhury, Luis-Carlos Tábara, Michele Frison, Stavroula Petridi, Patrick F Chinnery and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Developmental cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Mitochondrial curation for the next generation.Current opinion in genetics & development · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Rajini ChandrasegaramMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0XY, UK.
Sara GottardoMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK.
Abhilesh DhawanjewarMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0XY, UK.
Antony M Hynes-AllenMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0XY, UK.
Beitong GaoMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0XY, UK; Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
Suvagata Roy ChowdhuryMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK.
Luis-Carlos TábaraMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK.
Michele FrisonMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0XY, UK.
Stavroula PetridiMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0XY, UK.
Patrick F ChinneryMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0XY, UK.
Julien PrudentMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK.
Hansong MaSchool of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
Jelle van den AmeeleMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0XY, UK. Electronic address: jv361@cam.ac.uk.

Funding

Resource Component: Acquisition, maintenance and distribution of Drosophila stocksP40OD018537 · OD · TRUSTEES OF INDIANA UNIVERSITY · PI Annette L. Parks · 2014 to 2026
$13.5M
NIH HHS P40 OD018537Wellcome Trust
6 · The paper itself

Abstract

Mitochondrial DNA (mtDNA) exists in many copies per cell, with cell-to-cell variability in mutation load, which is known as heteroplasmy. Developmental and age-related expansion of heteroplasmic mtDNA mutations contributes to the pathogenesis of mitochondrial and neurodegenerative diseases. Here, we describe an approach for in situ sequence-specific detection of single mtDNA molecules (mtDNA-single-molecule fluorescent in situ hybridization [smFISH]). We apply this method to visualize and measure mtDNA and heteroplasmy levels in situ at single-cell resolution in whole-mount Drosophila tissue and cultured human cells. In Drosophila, we identify a somatic mtDNA bottleneck during neurogenesis. This amplifies heteroplasmy variability between neurons, as predicted by a mathematical bottleneck model, predisposing individual neurons to a high mutation load. However, both during neurogenesis and oogenesis, mtDNA segregation is accompanied by purifying selection, promoting wild-type (WT) over pathogenic mtDNA. mtDNA-smFISH thus elucidates how developmental cell-fate transitions, accompanied by changes in cell morphology, behavior, and metabolism, can shape the transmission and selection of deleterious mtDNA variants.

Indexed as

DNA, MitochondrialHeteroplasmyMitochondriaSingle Molecule ImagingAnimalsDrosophilaDrosophila melanogasterFemaleHumansIn Situ Hybridization, FluorescenceMutationNeurogenesisNeuronsOogenesisDNA, MitochondrialbottleneckDrosophilaheteroplasmymitochondriamitochondrial diseasemitochondrial DNAneurogenesisoogenesispurifying selectionsingle-molecule fluorescent in situ hybridization

Identifiers

PMID42127801
PMCPMC7619573

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.