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ATAD3A Limits Aortic Dissection via Mito-Lysosome Contacts and Lipoylation

GSE329337 Mus musculus (mouse) RNA-seq (gene expression) 24 samples Submitted 2026/06/20 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 24 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
24 samples: 7 × BAPN vs 6 × WT vs 6 × ATAD3A-KI-BAPN vs 5 × ATAD3A-KIGroups 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.
Summary (written by the submitters)
Background: Aortic aneurysm and dissection (AAD) is a fatal vascular emergency with limited mechanism-based therapies. The mitochondrial AAA⁺ ATPase ATAD3A, enriched at organelle contact sites, has been implicated in mitochondrial signaling, but its role in AAD remains unclear. Methods: AAD was induced in wild-type, ATAD3A knock-in (ATAD3A-KI), and vascular smooth muscle cell (VSMC)-specific knockdown (sh-ATAD3A) mice by 3-week β-aminopropionitrile monofumarate (BAPN) intake or 28-day angiotensin II (AngII) infusion via osmotic minipumps.
Read the full summary ↓
Aortic dilatation, dissection incidence, rupture-related mortality, and histology were assessed. VSMCs were stimulated with AngII in vitro. Mitochondrial function was evaluated using Seahorse bioenergetics, membrane potential assay, and Ca²⁺ imaging. ATAD3A-dihydrolipoamide s-succinyltransferase (DLST) interaction was examined by co-immunoprecipitation. Pharmacological modulation was performed with the copper chelator tetrathiomolybdate (TTM) and the lipoylation inhibitor Devimistat. Results: ATAD3A expression was upregulated in human thoracic aortic dissection samples and in BAPN-treated mouse aortas, with early downregulation then late upregulation in VSMCs. Systemic ATAD3A overexpression mitigated BAPN- and AngII-induced aortic dilatation, reduced dilation incidence, and improved survival, whereas VSMC-specific knockdown accelerated vascular pathology. Mechanistically, ATAD3A overexpression reduced mitochondria-lysosome contacts, limited mitochondrial Ca²⁺ influx, and suppressed the FDXR/FDX1/LIAS lipoylation pathway, decreasing DLST lipoylation and restraining cuproptosis, thereby preserving VSMC viability and delaying AAD progression. Pharmacological inhibition of cuproptosis using TTM or Devimistat attenuated disease severity in vivo. Conclusions: ATAD3A protects against AAD by coordinating organelle contact and metabolic signaling to restrain mitochondrial Ca²⁺ influx, NADPH flux, and DLST lipoylation-dependent cuproptosis in VSMCs. Targeting the ATAD3A-DLST-cuproptosis axis offers mechanistic insight and therapeutic potential for AAD.
This dataset
Open GSE329337 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 GSE329337_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 PRJNA1458662 and SRA study SRP695611. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
7 × BAPN vs 6 × WT vs 6 × ATAD3A-KI-BAPN vs 5 × ATAD3A-KI

Supports a between-group comparison across 24 samples.

How we read this: 4 replicated groups read from 24 sample titles; they account for 24 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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