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Adaptive antioxidant methionine accumulation in respiratory chain complexes explains the use of a deviant genetic code in mitochondria.

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.

SUBMITTER: Bender A

PROVIDER: S-EPMC2575448 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Adaptive antioxidant methionine accumulation in respiratory chain complexes explains the use of a deviant genetic code in mitochondria.

Bender Aline A Hajieva Parvana P Moosmann Bernd B

Proceedings of the National Academy of Sciences of the United States of America 20081022 43

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 fo ...[more]

PMID: 18946048

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Project description:This study was designed to compare the effect of methionine (Met) sources (DL-methionine [DLM] and DL-2-hydroxy-4-methylthio-butanoic acid [HMTBa]) and their supplementation levels on broiler growth performance and redox state. A 2 × 2 factorial arrangement was used with 2 sources (DLM and HMTBa) and 2 supplementation levels (0.05% and 0.25%) of Met. A total of 480 one-day-old broiler chicks were randomly divided into 4 treatments with 8 replicates per treatment (15 birds per replicate). The experiment lasted for 21 d. Broiler growth performance, redox capacity, redox-related genes expression, and Met transporters in different tissues were tested. Broilers fed high Met supplementation levels had improved (P < 0.05) body weight (BW), average daily gain (ADG) and feed conversion ratio (FCR). Similarly, broilers fed high Met levels had better (P < 0.05) antioxidant abilities in the serum, small intestine, and liver. Whereas, interactive effects (P < 0.05) were also observed between Met sources and levels. Compared with DLM, birds fed HMTBa diets had decreased (P < 0.05) total glutathione (T-GSH) and oxidized glutathione (GSSG) contents in duodenum, ileum, and liver. Similarly, broilers fed HMTBa supplemented diets had increased (P < 0.05) thioredoxin (Trx) gene expression in the duodenum and ileum, but decreased (P < 0.05) glutaredoxin (Grx), glutathione reductase (GSR), and glutathione synthetase (GSS) genes expression. Furthermore, lower gene expression of Na+ and Cl- dependent neutral and cationic amino acid transporter (ATB 0, + ), and Na+ dependent neutral amino acid transporter (B 0 AT) in the duodenum brush border, but higher gene expression of diamine acetyltransferase 1 (SAT1) and Na+-independent branched-chain and aromatic amino acid transporter (LAT1) in the jejunum and ileum basement membrane along with higher expression of the proton dependent monocarboxylate transporter 1 (MCT1) gene in the ileum were detected in birds fed HMTBa diets. In conclusion, DLM can be effectively used in glutathione synthesis to exert antioxidant functions, whereas HMTBa favors S-adenosylmethionine (SAM) synthesis and thus stimulates antioxidant-related genes expression.

Dataset Information

Adaptive antioxidant methionine accumulation in respiratory chain complexes explains the use of a deviant genetic code in mitochondria.

Publications

Adaptive antioxidant methionine accumulation in respiratory chain complexes explains the use of a deviant genetic code in mitochondria.

Similar Datasets

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