Nitrosative stress inhibits aminoacylation and editing activities of mitochondrial threonyl-tRNA synthetase by S-nitrosation.
Amino Acyl-tRNA Synthetases
/ genetics
Aminoacylation
/ genetics
Animals
Catalytic Domain
/ drug effects
HeLa Cells
Humans
Hydrogen Peroxide
/ chemistry
Kinetics
Mice
Mitochondria
/ enzymology
Nitrosation
/ genetics
Nitrosative Stress
/ genetics
Oxidation-Reduction
/ drug effects
Oxidative Stress
/ drug effects
Protein Processing, Post-Translational
/ drug effects
Threonine-tRNA Ligase
/ chemistry
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
09 07 2020
09 07 2020
Historique:
accepted:
22
05
2020
revised:
06
05
2020
received:
07
04
2020
pubmed:
3
6
2020
medline:
9
9
2020
entrez:
3
6
2020
Statut:
ppublish
Résumé
Structure and/or function of proteins are frequently affected by oxidative/nitrosative stress via posttranslational modifications. Aminoacyl-tRNA synthetases (aaRSs) constitute a class of ubiquitously expressed enzymes that control cellular protein homeostasis. Here, we found the activity of human mitochondrial (mt) threonyl-tRNA synthetase (hmtThrRS) is resistant to oxidative stress (H2O2) but profoundly sensitive to nitrosative stress (S-nitrosoglutathione, GSNO). Further study showed four Cys residues in hmtThrRS were modified by S-nitrosation upon GSNO treatment, and one residue was one of synthetic active sites. We analyzed the effect of modification at individual Cys residue on aminoacylation and editing activities of hmtThrRS in vitro and found that both activities were decreased. We further confirmed that S-nitrosation of mtThrRS could be readily detected in vivo in both human cells and various mouse tissues, and we systematically identified dozens of S-nitrosation-modified sites in most aaRSs, thus establishing both mitochondrial and cytoplasmic aaRS species with S-nitrosation ex vivo and in vivo, respectively. Interestingly, a decrease in the S-nitrosation modification level of mtThrRS was observed in a Huntington disease mouse model. Overall, our results establish, for the first time, a comprehensive S-nitrosation-modified aaRS network and a previously unknown mechanism on the basis of the inhibitory effect of S-nitrosation on hmtThrRS.
Identifiants
pubmed: 32484546
pii: 5850316
doi: 10.1093/nar/gkaa471
pmc: PMC7337905
doi:
Substances chimiques
Hydrogen Peroxide
BBX060AN9V
Amino Acyl-tRNA Synthetases
EC 6.1.1.-
Threonine-tRNA Ligase
EC 6.1.1.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6799-6810Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
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