ArticleProceedings of the National Academy of Sciences of the United States of America2008
Adaptive antioxidant methionine accumulation in respiratory chain complexes explains the use of a deviant genetic code in mitochondria.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 115 citations in OpenAlex.
- Restoring intracellular homeostasis disrupted by synthetic nanoassemblies.Nature chemical biology · 2026Article
- Molecular Complexity Constrained Early Amino Acid Recruitment into the Genetic Code.Genome biology and evolution · 2026Article
- Antioxidant evolution of fibrinogen: a crucial role of methionines.Biophysical reviews · 2025Review
- Tissue-specific molecular regulation of aging mechanisms with methionine restriction in mice and the potential role of methionine sulfoxide reductase.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- Epigenetic regulation of the respiratory chain by a mitochondrial distress-related redox signal.Frontiers in cell and developmental biology · 2025Article
- Order of amino acid recruitment into the genetic code resolved by last universal common ancestor's protein domains.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Balancing brain metabolic states during sickness and recovery sleep.The European journal of neuroscience · 2024Article
- Order of amino acid recruitment into the genetic code resolved by Last Universal Common Ancestor's protein domains.bioRxiv : the preprint server for biology · 2024Article
- Mitochondrial complex I inhibition triggers NADGeroScience · 2024Article
- Methionine oxidation of carbohydrate-active enzymes during white-rot wood decay.Applied and environmental microbiology · 2024Article
- Cysteine Is the Only Universally Affected and Disfavored Proteomic Amino Acid under Oxidative Conditions in Animals.Antioxidants (Basel, Switzerland) · 2024Article
- Sulfur Amino Acid Restriction alters mitochondrial function depending on tissue, sex, and Methionine sulfoxide reductase A (MsrA) status.Research square · 2023Article
- Common pathogenic bacteria-induced reprogramming of the host proteinogenic amino acids metabolism.Amino acids · 2023Review
- Optimal DL-Methionyl-DL-Methionine Supplementation Improved Intestinal Physical Barrier Function by Changing Antioxidant Capacity, Apoptosis and Tight Junction Proteins in the Intestine of Juvenile Grass Carp (Antioxidants (Basel, Switzerland) · 2022Article
- Probing the Role of Cysteine Thiyl Radicals in Biology: Eminently Dangerous, Difficult to Scavenge.Antioxidants (Basel, Switzerland) · 2022Review
- Functional and protective hole hopping in metalloenzymes.Chemical science · 2021Review
- Effects of recovery from short-term heat stress exposure on feed intake, plasma amino acid profiles, and metabolites in growing pigs.Journal of animal science and technology · 2021Article
- The Evolution of the Hallmarks of Aging.Frontiers in genetics · 2021Review
- Potential Association of Reactive Oxygen Species With Male Sterility in Peach.Frontiers in plant science · 2021Article
- Mitonuclear Interactions in the Maintenance of Mitochondrial Integrity.Life (Basel, Switzerland) · 2020Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Humans and most other animals use 2 different genetic codes to translate their hereditary information: the standard code for nuclear-encoded proteins and a modern variant of this code in mitochondria. Despite the pivotal role of the genetic code for cell biology, the functional significance of the deviant mitochondrial code has remained enigmatic since its first description in 1979. Here, we show that profound and functionally beneficial alterations on the encoded protein level were causative for the AUA codon reassignment from isoleucine to methionine observed in most mitochondrial lineages. We demonstrate that this codon reassignment leads to a massive accumulation of the easily oxidized amino acid methionine in the highly oxidative inner mitochondrial membrane. This apparently paradoxical outcome can yet be smoothly settled if the antioxidant surface chemistry of methionine is taken into account, and we present direct experimental evidence that intramembrane accumulation of methionine exhibits antioxidant and cytoprotective properties in living cells. Our results unveil that methionine is an evolutionarily selected antioxidant building block of respiratory chain complexes. Collective protein alterations can thus constitute the selective advantage behind codon reassignments, which authenticates the "ambiguous decoding" hypothesis of genetic code evolution. Oxidative stress has shaped the mitochondrial genetic code.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.