Glutamyl-tRNAGln amidotransferase is essential for mammalian. mitochondrial translation in vivo

被引：23

作者：

Echevarria, Lucia ^{[1
,2
]}

Clemente, Paula ^{[1
,2
]}

Hernandez-Sierra, Rosana ^{[1
,2
]}

Esther Gallardo, Maria ^{[1
,2
]}

Fernandez-Moreno, Miguel A. ^{[1
,2
]}

Garesse, Rafael ^{[1
,2
]}

机构：

[1] Univ Autonoma Madrid, Fac Med, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Inst Invest Biomed Alberto Sols UAM CSIC,Dept Bio, Madrid, Spain

[2] Inst Invest Sanitaria 12 Octubre i 12, Madrid, Spain

来源：

BIOCHEMICAL JOURNAL | 2014年 / 460卷

关键词：

glutamyl-tRNA(GIn) amidotransferase CAB (GatCAB); mitochondrial protein synthesis; mitochondrion; oxidative phosphorylation (OXPHOS); tRNA(GIn); RNA-DEPENDENT AMIDOTRANSFERASE; ELONGATION-FACTOR TU; PROTEIN-SYNTHESIS; ESCHERICHIA-COLI; GLN-TRNA(GLN); SUBUNIT; PATHWAY; GATCAB; CELLS;

D O I：

10.1042/BJ20131107

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Translational accuracy depends on the correct formation of aminoacyl-tRNAs, which, in the majority of cases, are produced by specific aminoacyl-tRNA synthetases that ligate each amino acid to its cognate isoaceptor tRNA Aminoacylation of tRNA(Gln), however, is performed by various mechanisms in different systems. Since no mitochondrial glutaminyl-tRNA synthetase has been identified to date in mammalian mitochondria, Gln-tRNA(Gln) has to be formed by an indirect mechanism in the organelle. It has been demonstrated that human mitochondria contain a non-discriminating glutamyl-tRNA synthetase and the heterotrimeric enzyme GatCAB (where Gat is glutamyl-tRNA(Gln) amidotransferase), which are able to catalyse the formation of Gln-tRNA(Gln) in vitro. In the present paper we demonstrate that mgatA (mouse GatA) interference in mouse cells produces a strong defect in mitochondrial translation without affecting the stability of the newly synthesized proteins. As a result, interfered cells present an impairment of the oxidative phosphorylation system and a significant increase in ROS (reactive oxygen species) levels. MS analysis of mitochondrial proteins revealed no glutamic acid found in the position of glutamines, strongly suggesting that misaminoacylated Glu-tRNA(Gln) is rejected from the translational apparatus to maintain the fidelity of mitochondrial protein synthesis in mammals.

引用

页码：91 / 101

页数：11

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