Conserved mitochondrial suppression across six eukaryotic species in spaceflight

A human-anchored, cross-species meta-analysis of spaceflight transcriptomics from the NASA Open Science Data Repository — asking which organelle-level responses are shared across a billion years of eukaryotic evolution.

CC BY 4.0FAIR NASA OSDROrthoDB v12 22 datasets6 species
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Headline: a conserved downregulation of mitochondrial genes — 49 orthologs suppressed, direction-consistent, across at least three of six species — pinpoints mitochondrial energy metabolism as a deeply conserved target of the spaceflight transcriptional response.

Abstract

Spaceflight induces transcriptomic changes across organisms, but the extent to which subcellular and metabolic pathways are conserved across species remains poorly understood. We performed a cross-species meta-analysis of 22 transcriptomic datasets from the NASA Open Science Data Repository spanning six eukaryotic species (Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Saccharomyces cerevisiae, and Arabidopsis thaliana), encompassing 20,333 differentially expressed genes. Using a human-anchored orthology matrix built from OrthoDB v12 (18,030 genes; 651 with orthologs in all six species), we mapped DEGs to 16 subcellular compartments and applied Fisher's combined probability test to identify conserved organelle-level responses. We report a striking conserved downregulation of mitochondrial genes: 49 orthologs show significant, direction-consistent suppression across at least three species (minimum Fisher FDR = 7.7×10⁻⁶⁸), including components of Complex III (CYC1), Complex IV (COX5B, COX6A2, COX6B2), ATP synthase (ATP5F1A, ATP5PD) and the TCA cycle (IDH3A/B/G). In contrast, peroxisome, lipid-droplet and Golgi genes show conserved upregulation. These findings identify mitochondrial energy metabolism as a deeply conserved target of the spaceflight transcriptional response.

Highlights

Six species, one anchor

22 OSDR datasets across 6 species mapped onto a human-anchored OrthoDB v12 orthology matrix (18,030 genes).

Conserved mito suppression

49 mitochondrial orthologs down-regulated across ≥3 species (Fisher FDR down to 7.7×10⁻⁶⁸) — the most robust conserved response.

Directional contrast

Mitochondrion, ER and cytoskeleton down; peroxisome, lipid particle and Golgi up.

Pathway resolution

KEGG overlays show NAD⁺-dependent OxPhos enzymes diverge by species while CoA-dependent TCA enzymes stay conserved.

Selected figures

Study overview: OSDR datasets and DEGs per species.
Fig 1 — Study overview: datasets and differentially expressed genes per species.
Signed organelle enrichment across species.
Fig 4 — Signed subcellular-organelle enrichment across the six species.
Conserved organelle schematic: mitochondrion downregulated across species.
Fig 5 — Conserved organelle responses; the mitochondrion (49 genes) is the most robustly conserved.

Data & code

Transcriptomic data derive from NASA OSDR / GeneLab (cite the individual OSD accessions); orthology from OrthoDB v12; pathways from KEGG. OSDR data remain subject to the NASA Open Data policy.