title: Protein-borne methionine residues as structural antioxidants in mitochondria.
abstract: Methionine is an oxidant-labile amino acid whose major oxidation products, methionine sulfoxides, can be readily repaired by various NADPH-dependent methionine sulfoxide reductases. Formally, the methionine oxidation-reduction circuit could act as a cellular antioxidant system, by providing a safe sink for oxidants that might cause much more damage if reacting otherwise. This concept is supported by focal experimental evidence; however, the global importance, scope and biochemical role of protein-borne methionine as an inbuilt macromolecular antioxidant have remained incompletely defined. In analyzing proteomic methionine usage on different levels of comparison, we find that protein methionine (i) is primarily an antioxidant of mitochondria, especially of the inner mitochondrial membrane, (ii) responds strongly to respiratory demands on an evolutionary timescale, (iii) acts locally, by selectively protecting its carrier protein, and (iv) might be utilized as a molecular predictor of aerobic metabolic rate in animals, to complement traditional markers like the presence of a respiratory pigment. Our data support the idea that proteins in need of a long lifespan or acting in dangerous environments may acquire massive structural alterations aimed at increasing their resistance to oxidation. Counterintuitively though, they sometimes do so by accumulating particularly labile rather than particularly stable building blocks, illustrating that the technical concept of cathodic protection is also employed by the animate nature.
authors: Evolutionary Biochemistry and Redox Medicine, Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, 55099, Mainz, Germany.
authors: Mario
authors: M
authors: Schindeldecker
authors: Bernd
authors: B
authors: Moosmann
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry*; D045222:Electron Transport Chain Complex Proteins / Q000737:chemistry; D004734:Energy Metabolism; D006801:Humans; D008715:Methionine / Q000737:chemistry*; D008928:Mitochondria / Q000737:chemistry* / Q000502:physiology; D008958:Models, Molecular; D018384:Oxidative Stress
chemical_list: D000975:Antioxidants; D045222:Electron Transport Chain Complex Proteins; D008715:Methionine