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Mitochondrial complex III-derived ROS amplify immunometabolic changes in astrocytes and promote dementia pathology

GSE304378 Mus musculus (mouse) RNA-seq (gene expression) 27 samples Submitted 2025/09/05 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 27 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
27 samples: 9 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 complex III-derived ROS amplify immunometabolic changes in astrocytes and promote dementia pathologyNature metabolism · 2025
Summary (written by the submitters)
Neurodegenerative disorders alter mitochondrial functions, including the production of reactive oxygen species (ROS). Mitochondrial complex III (CIII) generates ROS implicated in redox signaling, but its triggers, temporal dynamics, targets, and disease relevance are not clear. Using site-selective suppressors and genetic manipulations together with live mitochondrial ROS imaging and multiomic profiling, we found that CIII is a dominant source of ROS production in astrocytes exposed to neuropathology-related stimuli.
Read the full summary ↓
Astrocytic CIII-ROS production was dependent on nuclear factor-κB (NF-κB) and the mitochondrial sodium-calcium exchanger (NCLX) and caused oxidation of select cysteines within immune- and metabolism-associated proteins linked to neurological disease. CIII-ROS amplified metabolomic and pathology-associated transcriptional changes in astrocytes, with STAT3 activity as a major mediator, and facilitated neuronal toxicity. Therapeutic suppression of CIII-ROS in mice decreased dementia-linked tauopathy and neuroimmune cascades and extended lifespan. Our findings establish CIII-ROS as an important immunometabolic signal transducer and tractable therapeutic target in neurodegenerative disease.
Published in
Mitochondrial complex III-derived ROS amplify immunometabolic changes in astrocytes and promote dementia pathology
Barnett D, Zimmer TS, Booraem C et al. · Nature metabolism 2025 · PMID 41188644 · doi:10.1038/s42255-025-01390-y
This dataset
Open GSE304378 in finder → Find more mouse 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 GSE304378_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: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1301137 and SRA study SRP606258. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41188644) ↗
Study design
9 conditions, mostly in triplicate
Experiment 1, Primary mouse astrocyte, 6 hour… ×3 Experiment 1, Primary mouse astrocyte, 6 hour… ×3 Experiment 1, Primary mouse astrocyte, 6 hour… ×3 Experiment 1, Primary mouse astrocyte, 6 hour… ×3 Experiment 2, Primary mouse astrocyte, 6 hour… ×3 Experiment 2, Primary mouse astrocyte, 6 hour… ×3 Experiment 2, Primary mouse astrocyte, 6 hour… ×3 Experiment 2, Primary mouse astrocyte, 6 hour… ×3 +1 more

Supports a between-group comparison across 27 samples.

How we read this: 9 replicated groups read from 27 sample titles; they account for 27 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
Datasets on a similar topic

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