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Journal articles
The isolated carboxy-terminal domain of human mitochondrial leucyl-tRNA synthetase rescues the pathological phenotype of mitochondrial tRNA mutations in human cells.
Abstract : Mitochondrial (mt) diseases are multisystem disorders due to mutations in nuclear or mtDNA genes. Among the latter, more than 50% are located in transfer RNA (tRNA) genes and are responsible for a wide range of syndromes, for which no effective treatment is available at present. We show that three human mt aminoacyl-tRNA syntethases, namely leucyl-, valyl-, and isoleucyl-tRNA synthetase are able to improve both viability and bioenergetic proficiency of human transmitochondrial cybrid cells carrying pathogenic mutations in the mt-tRNA(Ile) gene. Importantly, we further demonstrate that the carboxy-terminal domain of human mt leucyl-tRNA synthetase is both necessary and sufficient to improve the pathologic phenotype associated either with these "mild" mutations or with the "severe" m.3243A>G mutation in the mt-tRNA(L)(eu(UUR)) gene. Furthermore, we provide evidence that this small, non-catalytic domain is able to directly and specifically interact in vitro with human mt-tRNA(Leu(UUR)) with high affinity and stability and, with lower affinity, with mt-tRNA(Ile). Taken together, our results sustain the hypothesis that the carboxy-terminal domain of human mt leucyl-tRNA synthetase can be used to correct mt dysfunctions caused by mt-tRNA mutations.
Cited literature [48 references]
https://hal-riip.archives-ouvertes.fr/pasteur-01168181
Contributor : Istituto Pasteur Fondazione Cenci Bolognetti <>
Submitted on : Thursday, June 25, 2015 - 1:35:15 PM
Last modification on : Wednesday, October 28, 2020 - 3:20:08 PM
Long-term archiving on: : Wednesday, September 16, 2015 - 12:21:06 AM
Contributor : Istituto Pasteur Fondazione Cenci Bolognetti <>
Submitted on : Thursday, June 25, 2015 - 1:35:15 PM
Last modification on : Wednesday, October 28, 2020 - 3:20:08 PM
Long-term archiving on: : Wednesday, September 16, 2015 - 12:21:06 AM
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emmm0006-0169.pdf
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