Zhang_2026_Proc.Natl.Acad.Sci.U.S.A_123_e2527470123

Membrane phospholipid peroxidation is a deleterious process in which reactive oxygen species (ROS) attack unsaturated fatty acids embedded in cell membranes, generating phospholipid hydroperoxides and triggering structural damage that can ultimately lead to cell death. While mammalian strategies to mitigate peroxidation, primarily through the combined activities of phospholipase A(2) (PLA(2)) and subsequent reduction of resultant fatty acid hydroperoxides with glutathione peroxidases/peroxiredoxins have been well characterized for more than two decades, mechanisms by which prokaryotes contend with this oxidative challenge remain poorly understood. Here, we report a phospholipid hydroperoxide elimination strategy mediated by the bifunctional enzyme PpLipO from the Antarctic sea-ice bacterium Pseudoalteromonas prydzensis. This enzyme comprises an N-terminal lipase domain and a C-terminal lipoyl peroxidase domain. Through synergistic action of these domains, PpLipO first hydrolyzes ROS-induced phospholipid hydroperoxides into fatty acid hydroperoxides via its lipase domain, then catalyzes their reduction to hydroxy fatty acids via the peroxidase domain. Comprehensive phylogenetic and structural analyses of the C-terminal peroxidase domain revealed its unique position within a distinct clade of the Ohr/OsmC family, known for their roles in organic hydroperoxide detoxification. Functional studies of PpLipO homologs in other marine bacteria, combined with metagenomic surveys, suggest that this strategy is widespread in global oceans, particular among polar marine bacteria. Altogether, our findings identify a prokaryotic phospholipid peroxidation repair mechanism that parallels the mammalian PLA(2) - peroxidase system, expanding our understanding of oxidative stress response across domains of life.