Elephant seal cells export iron and form lipid droplets to evade lipid peroxidation
- 1University of California, Berkeley
Abstract
Elephant seals are remarkable breath-hold divers, capable of remaining submerged for up to two hours during diving bouts. These dives entail repeated, extreme hypoxia/reoxygenation events that would induce severe lipid peroxidation and tissue dysfunction in most species. Here, we show that primary vascular endothelial cells derived from elephant seals resist oxidant-induced lipid peroxidation and cell death without relying on canonical lipid hydroperoxide scavenging. Comparative transcriptomic profiling across seal, human, and sheep cells identified transcriptional signatures of lipid metabolism and iron handling as uniquely regulated in seal cells following hydroperoxide exposure. Mechanistically, seal cells exhibit high constitutive levels of acyl-CoA synthetase long-chain family member 3 (ACSL3) alongside robust, seal-specific induction of the iron exporter ferroportin-1 (FPN1). Comparative lipidomic profiling revealed that seal cells are enriched in triglycerides and monounsaturated fatty acids. ACSL3 silencing and FPN1 inhibition each partially sensitized seal cells to lipid peroxidation, identifying lipid droplet biogenesis and active iron export as complementary but non-redundant axes of protection. Together, these data reveal a protective strategy based on lipid sequestration and iron export rather than hydroperoxide reduction, with implications for ischemia-reperfusion injury in non-diving mammals.
Related
- Hydroethanolic Montanoa bipinnatifida Leaf Extract Attenuates Acute Ethanol-Induced Gastric Mucosal Injury in Female CD-1 Mice: Associations with Lipid Peroxidation and IL-1β Expression
- Constitutive PI3K-AKT activation promotes steatohepatitis through de novo lipogenesis despite enhanced mitochondrial β-oxidation, essential fatty acid depletion and reduced lipid peroxidation
- Mitochondria Bound to Lipid Droplets Have Unique Bioenergetics, Composition, and Dynamics that Support Lipid Droplet Expansion
- Biochemical Remodeling of Purine Metabolism and Lipid Peroxidation Across Thyroid Disease Phenotypes.
- The STAT1–IRF1–ACSL4 axis drives peritoneal fibrosis and ferroptosis via lipid peroxidation-dependent mechanisms
BibTeX
@misc{allen2026elephant,
title = {{Elephant seal cells export iron and form lipid droplets to evade lipid peroxidation}},
author = {K. N. Allen and E. R. Piotrowski and D. D. Moreno-Santillan and A. Li and D. Luong and V. E. Foley and C. T. del Real and J. P. Vazquez-Medina},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.10.744012},
url = {https://www.biorxiv.org/content/10.64898/2026.08.10.744012v2},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Elephant seal cells export iron and form lipid droplets to evade lipid peroxidation
AU - K. N. Allen
AU - E. R. Piotrowski
AU - D. D. Moreno-Santillan
AU - A. Li
AU - D. Luong
AU - V. E. Foley
AU - C. T. del Real
AU - J. P. Vazquez-Medina
PY - 2026
DA - 2026/08/10
PB - bioRxiv
DO - 10.64898/2026.08.10.744012
UR - https://www.biorxiv.org/content/10.64898/2026.08.10.744012v2
AB - Elephant seals are remarkable breath-hold divers, capable of remaining submerged for up to two hours during diving bouts. These dives entail repeated, extreme hypoxia/reoxygenation events that would induce severe lipid peroxidation and tissue dysfunction in most species. Here, we show that primary vascular endothelial cells derived from elephant seals resist oxidant-induced lipid peroxidation and cell death without relying on canonical lipid hydroperoxide scavenging. Comparative transcriptomic profiling across seal, human, and sheep cells identified transcriptional signatures of lipid metabolism and iron handling as uniquely regulated in seal cells following hydroperoxide exposure. Mechanistically, seal cells exhibit high constitutive levels of acyl-CoA synthetase long-chain family member 3 (ACSL3) alongside robust, seal-specific induction of the iron exporter ferroportin-1 (FPN1). Comparative lipidomic profiling revealed that seal cells are enriched in triglycerides and monounsaturated fatty acids. ACSL3 silencing and FPN1 inhibition each partially sensitized seal cells to lipid peroxidation, identifying lipid droplet biogenesis and active iron export as complementary but non-redundant axes of protection. Together, these data reveal a protective strategy based on lipid sequestration and iron export rather than hydroperoxide reduction, with implications for ischemia-reperfusion injury in non-diving mammals.
ER -