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Fig. 1 | Journal of Neurodevelopmental Disorders

Fig. 1

From: Mitochondrial aminoacyl-tRNA synthetase disorders: an emerging group of developmental disorders of myelination

Fig. 1

Effects of AARS2, EARS2, and DARS2 mutations on mitochondrial translation and respiratory chain complex function. Human mt-aaRSs are encoded in the nucleus, synthesized in the cytosol, and delivered and imported into the mitochondria. To facilitate mitochondrial translation, the 19 mt-aaRSs catalyze the specific attachment of each amino acid onto the cognate tRNA(s). Specifically, AARS2 attaches alanine, EARS2 attaches glutamate, and DARS2 attaches aspartate. The molecular structures for AARS2, EARS2, and DARS2 are represented and the chromosomal location of the genes is listed. The EARS2 structure has not yet been determined. Mitochondrial translation synthesizes 13 proteins that, together with 84 additional nucleus-encoded proteins, form the five respiratory chain complexes. Thus, mt-aaRSs play a key role in cellular energy production, and mutations in mt-aaRSs often involve the central nervous system. In AARS-2 ovario-leukodystrophy (LD), LTBL, and LBSL, the effects of pathogenic variants at the cellular level are incompletely described. However, for all three disorders, there is a variable reduction but not complete absence of protein and reduced enzyme activity [6,7,8,9,10]. For AARS2 ovario-LD and LTBL, there is a subsequent RCC dysfunction, which has not yet been detected in LBSL patient cells [6,7,8,9,10]; oxygen consumption rate (OCR) and mitochondrial respiratory rate (MRR)

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