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Protein-borne methionine residues as structural antioxidants in mitochondria

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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.

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Article 25 November 2021

Sujatha Thankeswaran Parvathy, Varatharajalu Udayasuriyan & Vijaipal Bhadana

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Authors and Affiliations

  1. Evolutionary Biochemistry and Redox Medicine, Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, 55099, Mainz, Germany

    Mario Schindeldecker & Bernd Moosmann

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  1. Mario Schindeldecker
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  2. Bernd Moosmann
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Correspondence to Bernd Moosmann.

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Handling Editor: F. Galli.

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Schindeldecker, M., Moosmann, B. Protein-borne methionine residues as structural antioxidants in mitochondria. Amino Acids 47, 1421–1432 (2015). https://doi.org/10.1007/s00726-015-1955-8

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