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Global stabilization of the mitochondrial proteome is associated with extreme anoxia tolerance in Austrofundulus limnaeus WS40NE cells

BMC Biol. 2026 Jul 6. doi: 10.1186/s12915-026-02674-9. Online ahead of print.

ABSTRACT

BACKGROUND: Austrofundulus limnaeus is an extremophile vertebrate native to small temporary ponds of Venezuela. Embryos of A. limnaeus must survive variable and often extreme conditions, including long periods of anoxia. Neuroepithelial cells derived from these embryos, WS40NE cells, provide a unique tool to understand how the proteome changes in response to anoxic stress.

RESULTS: Using label-free proteomics, 19,604 peptides and 3487 proteins were quantified in normoxic, 4d anoxic, and 24 h recovery WS40NE cells. Of these, 2612 proteins (74.9%) were statistically significantly differentially abundant in at least one comparison: 1988 comparing normoxia to 4 days anoxia (57.0%), 923 comparing 4 days anoxia to 24 h recovery (26.5%), and 1814 comparing normoxia to 24 h recovery (52.0%). Further, interaction networks of proteins with similar expression patterns suggest that relative mitochondrial capacity may increase during anoxia, including upregulation and/or preferred stabilization of proteins involved in mitochondrial metabolism and mitochondrial transcription and translation. This is in sharp contrast to trends in proteins that support cytoplasmic translation.

CONCLUSIONS: These data support an active role for mitochondria in mediating the survival of the anoxia-tolerant WS40NE cell line and highlight the value of this non-traditional vertebrate model for uncovering novel mechanisms of cellular resilience.

PMID:42410428 | DOI:10.1186/s12915-026-02674-9

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