GEO series

Mitochondrial membrane hyperpolarization modulates nuclear DNA methylation and gene expression through phospholipid remodeling [RNA-Seq]

GSE295296 Homo sapiens (human) DNA methylation 18 samples Submitted 2025/04/22 Platform GPL24676

At a glance

DNA methylation · human · 18 samples

What it is: DNA methylationChemical marks on DNA that help switch genes on or off.
Organism: Homo sapiens (human)
Samples: 18 samples: 6 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Mitochondrial membrane hyperpolarization modulates nuclear DNA methylation and gene expression through phospholipid remodelingNature communications · 2025

Summary (written by the submitters)

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.

Read the full summary ↓

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.

Published in

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

Mori MP, Lozoya OA, Brooks AM et al. · Nature communications 2025 · PMID 40301431 · doi:10.1038/s41467-025-59427-5

This dataset

Open GSE295296 in finder → Find more human RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE295296_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Look for beta-value tables or raw IDAT files among the supplementary files.

Also filed as BioProject PRJNA1254136 and SRA study SRP580475. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40301431) ↗

Study design

6 conditions, mostly in triplicate

WT cells, seq run NOVO0082, ×3 IF1-KO cells, seq run NOVO0082, ×3 IF1-KO cells + GFP, seq run NOVO0082, ×3 IF1-KO rescue cells + GFP, seq run NOVO0082, ×3 IF1-KO cells, seq run NOVO0502, ×3 IF1-KO cells, UCP4 plasmid,, seq run NOVO0502, ×3

Supports a between-group comparison across 18 samples.

How we read this: 6 replicated groups read from 18 sample titles; they account for 18 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8944983 WT cells, seq run NOVO0082, rep1 WT cells, seq run NOVO0…
GSM8944984 WT cells, seq run NOVO0082, rep2 WT cells, seq run NOVO0…
GSM8944985 WT cells, seq run NOVO0082, rep3 WT cells, seq run NOVO0…
GSM8944986 IF1-KO cells, seq run NOVO0082, rep1 IF1-KO cells, seq run N…
GSM8944987 IF1-KO cells, seq run NOVO0082, rep2 IF1-KO cells, seq run N…
GSM8944988 IF1-KO cells, seq run NOVO0082, rep3 IF1-KO cells, seq run N…
GSM8944989 IF1-KO cells + GFP, seq run NOVO0082, rep1 IF1-KO cells + GFP, seq…
GSM8944990 IF1-KO cells + GFP, seq run NOVO0082, rep2 IF1-KO cells + GFP, seq…
GSM8944991 IF1-KO cells + GFP, seq run NOVO0082, rep3 IF1-KO cells + GFP, seq…
GSM8944992 IF1-KO rescue cells + GFP, seq run NOVO0082, rep1 IF1-KO rescue cells + G…
GSM8944993 IF1-KO rescue cells + GFP, seq run NOVO0082, rep2 IF1-KO rescue cells + G…
GSM8944994 IF1-KO rescue cells + GFP, seq run NOVO0082, rep3 IF1-KO rescue cells + G…
GSM8944995 IF1-KO cells, seq run NOVO0502, rep1 IF1-KO cells, seq run N…
GSM8944996 IF1-KO cells, seq run NOVO0502, rep2 IF1-KO cells, seq run N…
GSM8944997 IF1-KO cells, seq run NOVO0502, rep3 IF1-KO cells, seq run N…
GSM8944998 IF1-KO cells, UCP4 plasmid,, seq run NOVO0502, rep1 IF1-KO cells, UCP4 plas…
GSM8944999 IF1-KO cells, UCP4 plasmid,, seq run NOVO0502, rep2 IF1-KO cells, UCP4 plas…
GSM8945000 IF1-KO cells, UCP4 plasmid,, seq run NOVO0502, rep3 IF1-KO cells, UCP4 plas…

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.