González-Serrano L E, Karim L, Pierre F, Schwenzer H, Rotig A, Munnich A, Sissler M
Three human aminoacyl-tRNA synthetases have distinct sub-mitochondrial localizations that are unaffected by disease-associated mutations Article de journal
Dans: J Biol Chem, vol. 293, no. 35, p. 13604-13615, 2018, ISBN: 30006346.
Résumé | Liens | BibTeX | Étiquettes: aminoacyl tRNA synthetase dual-localization human leukodystrophy membrane-anchored mitochondria mitochondrial disorder neurodegenerative disease pontocerebellar hypoplasia translation, SISSLER, Unité ARN
@article{,
title = {Three human aminoacyl-tRNA synthetases have distinct sub-mitochondrial localizations that are unaffected by disease-associated mutations},
author = {L E González-Serrano and L Karim and F Pierre and H Schwenzer and A Rotig and A Munnich and M Sissler},
url = {https://www.ncbi.nlm.nih.gov/pubmed/30006346?dopt=Abstract},
doi = {10.1074/jbc.RA118.003400},
isbn = {30006346},
year = {2018},
date = {2018-01-01},
journal = {J Biol Chem},
volume = {293},
number = {35},
pages = {13604-13615},
abstract = {Human mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) are key enzymes in the mitochondrial protein translation system and catalyze the charging of amino acids on their cognate tRNAs. Mutations in their nuclear genes are associated with pathologies having a broad spectrum of clinical phenotypes, but with no clear molecular mechanism(s). For example, mutations in the nuclear genes encoding mt-AspRS and mt-ArgRS are correlated with the moderate neurodegenerative disorder leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) and with the severe neurodevelopmental disorder pontocerebellar hypoplasia type 6 (PCH6), respectively. Previous studies have shown no or only minor impacts of these mutations on the canonical properties of these enzymes, indicating that the role of the mt-aaRSs in protein synthesis is mostly not affected by these mutations, but their effects on the mitochondrial localizations of aaRSs remain unclear. Here, we demonstrate that three human aaRSs, mt-AspRS, mt-ArgRS, and LysRS, each have a specific sub-mitochondrial distribution, with mt-ArgRS being exclusively localized in the membrane, LysRS exclusively in the soluble fraction, and mt-AspRS being present in both. Chemical treatments revealed that mt-AspRs is anchored in the mitochondrial membrane through electrostatic interactions, whereas mt-ArgRS uses hydrophobic interactions. We also report that novel mutations in mt-AspRS and mt-ArgRS genes from individuals with LBSL and PCH6, respectively, had no significant impact on the mitochondrial localizations of mt-AspRS and mt-ArgRS. The variable sub-mitochondrial locations for these three mt-aaRSs strongly suggest the existence of additional enzyme properties, requiring further investigation to unravel the mechanisms underlying the two neurodegenerative disorders.},
keywords = {aminoacyl tRNA synthetase dual-localization human leukodystrophy membrane-anchored mitochondria mitochondrial disorder neurodegenerative disease pontocerebellar hypoplasia translation, SISSLER, Unité ARN},
pubstate = {published},
tppubtype = {article}
}