Evidence map›Paper›PMID 38347148›Full record

ArticleNature structural & molecular biology2024

Single-nucleoid architecture reveals heterogeneous packaging of mitochondrial DNA.

R Stefan Isaac, Thomas W Tullius, Katja G Hansen, Danilo Dubocanin, Mary Couvillion, Andrew B Stergachis, L Stirling Churchman

Open access · greenAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
11.5field-weighted citation impact, top 1% of its field
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

31 citing papers in PubMed, 50 citations in OpenAlex.

  1. Review
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  4. TFAM organizes DNA into compact higher order structures.bioRxiv : the preprint server for biology · 2026
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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

7 authors at 3 institutions in 1 country.

R Stefan IsaacDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-5723-3882
Thomas W Tullius *Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Katja G Hansen *Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Danilo DubocaninDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA.
Mary CouvillionDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Andrew B StergachisDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA. absterga@uw.edu.ORCID http://orcid.org/0000-0002-1299-3674
L Stirling ChurchmanDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. churchman@genetics.med.harvard.edu.ORCID http://orcid.org/0000-0003-3888-2574
Harvard University · USUniversity of Washington · USUniversity of Washington Medical Center · US

Funding

Investigating the contribution of non-coding genetic variation to rare disordersDP5OD029630 · OD · UNIVERSITY OF WASHINGTON · PI STERGACHIS, ANDREW BEN · 2020 to 2024
$1.9M
Nuclear-mitochondrial co-regulation during mitochondrial biogenesisR01GM123002 · NIGMS · HARVARD MEDICAL SCHOOL · PI CHURCHMAN, LEE STIRLING · 2017 to 2020
$1.3M
The 3D architecture of the mitochondrial nucleoid and its role in organelle regulationF32GM130028 · NIGMS · HARVARD MEDICAL SCHOOL · PI ISAAC, RICHARD STEFAN · 2018 to 2022
$223k
NIGMS NIH HHS F32 GM130028NIGMS NIH HHS R01 GM123002NIH HHS DP5 OD029630
6 · The paper itself

Abstract

Cellular metabolism relies on the regulation and maintenance of mitochondrial DNA (mtDNA). Hundreds to thousands of copies of mtDNA exist in each cell, yet because mitochondria lack histones or other machinery important for nuclear genome compaction, it remains unresolved how mtDNA is packaged into individual nucleoids. In this study, we used long-read single-molecule accessibility mapping to measure the compaction of individual full-length mtDNA molecules at near single-nucleotide resolution. We found that, unlike the nuclear genome, human mtDNA largely undergoes all-or-none global compaction, with most nucleoids existing in an inaccessible, inactive state. Highly accessible mitochondrial nucleoids are co-occupied by transcription and replication components and selectively form a triple-stranded displacement loop structure. In addition, we showed that the primary nucleoid-associated protein TFAM directly modulates the fraction of inaccessible nucleoids both in vivo and in vitro, acting consistently with a nucleation-and-spreading mechanism to coat and compact mitochondrial nucleoids. Together, these findings reveal the primary architecture of mtDNA packaging and regulation in human cells.

Indexed as

DNA, MitochondrialMitochondrial ProteinsHumansMitochondriaDNA, MitochondrialMitochondrial Proteins

Identifiers

PMID38347148
PMCPMC11370055
OpenAlexW4391747306

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.