Evidence map›Paper›PMID 41431444›Full record

ArticleEpigenomics2026

Mitochondrial DNA copy number reduction via

Phyo W Win, Julia Nguyen, Elly H Shin, Tyler S Nagano, Brent Selimi, Katie Hong, Anahita M Meybodi, Bradley P Yates, Emma V Burke, David E Carter and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Epigenomics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Phyo W WinDepartment of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Julia NguyenDepartment of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Elly H ShinDepartment of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Tyler S NaganoDepartment of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Brent SelimiDepartment of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Katie HongMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Anahita M MeybodiDepartment of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Bradley P YatesMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Emma V BurkeMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
David E CarterLondon Regional Genomics Centre, Robarts Research Institute, London, Ontario, Canada.
Gregory A NewbyMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Charles NewcombMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Dan E ArkingMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Christina A CastellaniDepartment of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.

Funding

Mitochondrial DNA heteroplasmy and risk for atherosclerotic cardiovascular disease (ASCVD)R01HL144569 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI ARKING, DAN E · 2019 to 2022
$3.1M
Mitochondrial Function and Multiomics in Aging-related Disease: Identifying Novel Biomarkers and Causal RelationshipsR01AG085753 · NIA · JOHNS HOPKINS UNIVERSITY · PI Dan E Arking · 2024 to 2026
$2.0M
In vivo precision genome editing to correct genetic diseaseR00HL163805 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI NEWBY, GREGORY A. · 2023 to 2025
$747k
NHLBI NIH HHS R00 HL163805NHLBI NIH HHS R01 HL144569NIA NIH HHS R01 AG085753
6 · The paper itself

Abstract

aimsMitochondrial DNA copy number (mtDNA-CN) is associated with several age-related chronic diseases and is a predictor of all-cause mortality. Here, we examine site-specific differential nuclear DNA (nDNA) methylation and differential gene expression resulting from in vitro reduction of mtDNA-CN to uncover shared genes and biological pathways mediating the effect of mtDNA-CN on disease. MATERIALS AND

methodsEpigenome and transcriptome profiles were generated for three independent human embryonic kidney (HEK293T) cell lines harboring a mitochondrial transcription factor A (TFAM) knockout generated via CRISPR-Cas9, and matched control lines.

resultsWe identified 2924 differentially methylated sites, 67 differentially methylated regions, and 102 differentially expressed genes associated with mtDNA-CN. Integrated analysis uncovered 24 Gene-CpG pairs. GABA

conclusionsWe demonstrate that mitochondrial DNA variation signals to the nuclear DNA epigenome and transcriptome and may lead to nuclear remodeling relevant to development, aging, and complex disease.

Indexed as

Cell NucleusDNA-Binding ProteinsDNA Copy Number VariationsDNA, MitochondrialEpigenomeMitochondrial ProteinsTranscription FactorsTranscriptomeDNA MethylationEpigenesis, GeneticGene Knockout TechniquesHEK293 CellsHumansDNA-Binding ProteinsDNA, MitochondrialMitochondrial ProteinsTFAM protein, humanTranscription FactorsepigenomeMitochondriamitochondrial DNAmitochondrial DNA copy numbertranscriptome

Identifiers

PMID41431444
PMCPMC12826749

What OpenQuestion holds

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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.