Evidence map›Paper›PMID 40301431›Full record

ArticleNature communications2025

Mitochondrial membrane hyperpolarization modulates nuclear DNA methylation and gene expression through phospholipid remodeling.

Mateus Prates Mori, Oswaldo A Lozoya, Ashley M Brooks, Carl D Bortner, Cristina A Nadalutti, Birgitta Ryback, Brittany P Rickard, Marta Overchuk, Imran Rizvi, Tatiana Rogasevskaia and 4 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Antioxidants (Basel, Switzerland) · 2026
    Article
  8. Article
  9. Article
  10. Mitochondrial Adaptation to Mechanical Stress in Cardiac Ageing and Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Oxidative Phosphorylation in Uncoupled Mitochondria.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  16. Review
  17. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Mateus Prates MoriMechanistic Toxicology Branch, Division of Translational Toxicology, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Durham, NC, USA.ORCID http://orcid.org/0000-0003-1349-6378
Oswaldo A LozoyaGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Durham, NC, USA.ORCID http://orcid.org/0000-0001-6779-7382
Ashley M BrooksBiostatistics and Computational Biology Branch, Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Durham, NC, USA.
Carl D BortnerFlow Cytometry Center, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Durham, NC, USA.
Cristina A NadaluttiMechanistic Toxicology Branch, Division of Translational Toxicology, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Durham, NC, USA.
Birgitta RybackDana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Brittany P RickardCurriculum in Toxicology & Environmental Medicine, University of North Carolina (UNC), Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-6112-1290
Marta OverchukDepartment of Biomedical Engineering, North Carolina State University, Raleigh, NC, USA.
Imran RizviDepartment of Biomedical Engineering, North Carolina State University, Raleigh, NC, USA.
Tatiana RogasevskaiaDepartment of Biology, Mount Royal University, Calgary, AB, Canada.
Kai Ting HuangMitoCare Center, Department of Pathology and Genomic Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
Prottoy HasanMitoCare Center, Department of Pathology and Genomic Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
György HajnóczkyMitoCare Center, Department of Pathology and Genomic Medicine, Thomas Jefferson University, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-3813-2570
Janine H SantosMechanistic Toxicology Branch, Division of Translational Toxicology, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Durham, NC, USA. janine.santos@nih.gov.ORCID http://orcid.org/0000-0001-6384-3070

Funding

TOXICOLOGYT32ES007126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ILONA JASPERS, Bernard E. Weissman · 1985 to 2026
$13.0M
CAROLINA CANCER NANOTECHNOLOGY TRAINING PROGRAM (C-CNTP)T32CA196589 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Gaorav P. Gupta, ALEXANDER V KABANOV · 2015 to 2026
$4.5M
ER-mitochondrial communication in calcium signaling, energy metabolism and liver diseaseR01DK125897 · NIDDK · THOMAS JEFFERSON UNIVERSITY · PI CSORDAS, GYORGY, HAJNOCZKY, GYORGY · 2021 to 2025
$2.7M
Targeting Fluid Stress-induced Chemoresistance in a 3D Carcinomatosis Perfusion Model Using Mechanism-based Photo-immunoconjugate NanoparticlesR01CA256710 · NCI · UNIV OF MARYLAND, COLLEGE PARK · PI Huang Chiao Huang, Imran Rizvi · 2023 to 2026
$2.2M
Mitochondrial Calcium Uniporter in Signaling and DynamicsR01GM151536 · NIGMS · THOMAS JEFFERSON UNIVERSITY · PI Gyorgy Hajnoczky · 2023 to 2026
$1.7M
Mount Royal University (MRU) IRGFNCI NIH HHS R01 CA256710NCI NIH HHS T32 CA196589NIDDK NIH HHS R01 DK125897NIEHS NIH HHS T32 ES007126NIGMS NIH HHS R01 GM151536U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences (NIEHS) Intramural Program
6 · The paper itself

Abstract

Maintenance of the mitochondrial inner membrane potential (ΔΨm) is critical for many aspects of mitochondrial function. While ΔΨm loss and its consequences are well studied, little is known about the effects of mitochondrial hyperpolarization. In this study, we used cells deleted of ATP5IF1 (IF1), a natural inhibitor of the hydrolytic activity of the ATP synthase, as a genetic model of increased resting ΔΨm. We found that the nuclear DNA hypermethylates when the ΔΨm is chronically high, regulating the transcription of mitochondrial, carbohydrate and lipid genes. These effects can be reversed by decreasing the ΔΨm and recapitulated in wild-type (WT) cells exposed to environmental chemicals that cause hyperpolarization. Surprisingly, phospholipid changes, but not redox or metabolic alterations, linked the ΔΨm to the epigenome. Sorted hyperpolarized WT and ovarian cancer cells naturally depleted of IF1 also showed phospholipid remodeling, indicating this as an adaptation to mitochondrial hyperpolarization. These data provide a new framework for how mitochondria can impact epigenetics and cellular biology to influence health outcomes, including through chemical exposures and in disease states.

Indexed as

Cell NucleusDNA MethylationMembrane Potential, MitochondrialMitochondrial MembranesPhospholipidsAnimalsCell Line, TumorFemaleHumansMiceMitochondriaMitochondrial Proton-Translocating ATPasesMitochondrial Proton-Translocating ATPasesPhospholipids

Identifiers

PMID40301431
PMCPMC12041266

What Socratic holds

Textmetadata
LicenceCC BY
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.