Jean-Paul Bourdineaud Ricardo B. Oliveira Sandra LF Sarrazin David P. Krabbenhoft Collin A. Eagles-Smith Joshua T. Ackerman Robin Stewart Christian Ward-Deitrich M Estela del Castillo Busto Heidi Goenaga-Infante Aude Wack Marius Retegan Blanka Detlefs Pieter Glatzel Paco Bustamante Kathryn L. Nagy Brett Poulin Alain Manceau 2021 Toxicity of methylmercury (MeHg) to wildlife and humans results from its binding to cysteine residues of proteins, forming MeHg-cysteinate (MeHgCys) complexes that hinder biological functions. MeHgCys complexes can be detoxified in vivo, yet how this occurs is unknown. We report that MeHgCys complexes are transformed into selenocysteinate (Hg(Sec)4) complexes in multiple animals from two phyla (a waterbird, freshwater fish, and earthworms) sampled in different geographical areas and contaminated by different Hg sources. In addition, high energy-resolution X-ray absorption spectroscopy and chromatography-ICP mass spectrometry of the waterbird liver support the binding of Hg(Sec)4 to selenoprotein P and biomineralization of Hg(Sec)4 to chemically inert nanoparticulate mercury selenide (HgSe). The results provide a foundation for understanding mercury detoxification in higher organisms, and suggest that the identified MeHgCys to Hg(Sec)4 demethylation pathway is common in nature. application/pdf 10.1021/acs.est.0c04948 en American Chemical Society Demethylation of methylmercury in bird, fish, and earthworm article