Amino Acids

, Volume 47, Issue 7, pp 1421–1432 | Cite as

Protein-borne methionine residues as structural antioxidants in mitochondria

  • Mario Schindeldecker
  • Bernd MoosmannEmail author
Original Article


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.


Antioxidant Cathodic protection Metabolic rate Methionine oxidation Oxidative stress Respiratory chain complex 


Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  1. 1.Evolutionary Biochemistry and Redox Medicine, Institute for PathobiochemistryUniversity Medical Center of the Johannes Gutenberg UniversityMainzGermany

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