Evidence map›Paper›PMID 41759705›Full record

ArticleExperimental cell research2026

Transcriptomic analysis of cells following decreased mitochondrial DNA-copy number reveals compensatory mechanisms in mitochondrial DNA replication and cellular energetics.

Jiaqi Xie, Phyo W Win, Charles Newcomb, Shaopeng Zeng, Christina A Castellani, Dan E Arking

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Experimental cell research, 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. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Jiaqi XieMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Phyo W WinDepartment of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
Charles NewcombMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Shaopeng ZengMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Christina A CastellaniMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada; Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada; Children's Health Research Institute, Lawson Research Institute, London, ON, Canada. Electronic address: arking@jhmi.edu.
Dan E ArkingMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Funding

Human Mitochondrial Variation and Sudden Cardiac Arrest Risk and ResuscitationR01HL170579 · JOHNS HOPKINS UNIVERSITY · 2025 to 2025
$716k
Mitochondrial Function and Multiomics in Aging-related Disease: Identifying Novel Biomarkers and Causal RelationshipsR01AG085753 · JOHNS HOPKINS UNIVERSITY · 2025 to 2025
$662k
Functional Characterization of Mitochondrial Genome Nonsense MutationsR21AG082401 · JOHNS HOPKINS UNIVERSITY · 2025 to 2025
$205k
NHLBI NIH HHS R01 HL144569NHLBI NIH HHS R01 HL170579NIA NIH HHS R01 AG085753NIA NIH HHS R21 AG082401
6 · The paper itself

Abstract

Mitochondrial DNA copy number (mtDNA-CN) is a metric of mitochondrial function that has been associated with a variety of diseases including cardiovascular disease and all-cause mortality. To investigate genes and pathways affected by mtDNA-CN variation, we perturbed HEK 293T cells with ethidium bromide to deplete mtDNA. Using RNASeq and methylation microarrays, we evaluated transcriptomic and methylomic changes in treated cell lines. We observed an 8-fold decrease in mtDNA-CN and compensatory shifts in mitochondrial transcription to support mtDNA replication. Nuclear transcriptomic and methylomic analysis highlighted changes in metabolic pathways, including oxidative phosphorylation and canonical glycolysis. Longitudinal analyses revealed that the identified genes and pathways have different response timing, with nuclear response lagging behind mitochondrial response. These findings further elucidate the mechanisms behind mtDNA maintenance and responses to cellular energetics as well as mitochondrial-nuclear crosstalk dynamics.

Indexed as

DNA Copy Number VariationsDNA, MitochondrialDNA ReplicationEnergy MetabolismMitochondriaTranscriptomeDNA MethylationGene Expression ProfilingGlycolysisHEK293 CellsHumansOxidative PhosphorylationDNA, MitochondrialGlycolysisMethylomeMito-nuclear crosstalkmtDNA replicationOxidative phosphorylationTranscriptome

Identifiers

PMID41759705
PMCPMC13000920

What Socratic 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 Socratic graph.