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The m.3243A>G mutation within the mitochondrial mt-tRNALeu(UUR) gene is the most prevalent variant linked to mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome. This pathogenic mutation causes severe impairment of mitochondrial protein synthesis due to alterations of the mutated tRNA, such as reduced aminoacylation and a lack of post-transcriptional modification. In transmitochondrial cybrids, overexpression of human mitochondrial leucyl-tRNA synthetase (LARS2) has proven effective in rescuing the phenotype associated with m.3243A>G substitution. The rescuing activity resides in the carboxy-terminal domain (Cterm) of the enzyme; however, the precise molecular mechanisms underlying this process have not been fully elucidated. To deepen our knowledge on the rescuing mechanisms, we demonstrated the interactions of the Cterm with mutated mt-tRNALeu(UUR) and its precursor in MELAS cybrids. Further, the effect of Cterm expression on mitochondrial functions was evaluated. We found that Cterm ameliorates de novo mitochondrial protein synthesis, whilst it has no effect on mt-tRNALeu(UUR) steady-state levels and aminoacylation. Despite the complete recovery of cell viability and the increase in mitochondrial translation, Cterm-overexpressing cybrids were not able to recover bioenergetic competence. These data suggest that, in our MELAS cell model, the beneficial effect of Cterm may be mediated by factors that are independent of the mitochondrial bioenergetics.

Fig. 2 Phylogenetic tree of ITS containing region describing the evolutionary relationships among different geographical populations of Pratylenchus penetrans and other Pratylenchus species, using Maximum Likelihood (ML) method. Branch lengths are proportional to the distances as derived from the distance matrix obtained using the GTR method with the invariant site plus gamma options. Numbers at nodes indicate bootstrap values -Legend of Fig. 3: The correct legend for Fig. 3 reported in the paper is erroneously labeled as Fig. 4. The correct legend should be read: Fig. 3 Phylogenetic tree of D2-D3 expansion domains describing the evolutionary relationships among different geographical populations of Pratylenchus penetrans and other Pratylenchus species, using Maximum Likelihood (ML) method. Branch lengths are proportional to the distances as derived from the distance matrix obtained using the GTR method with the invariant site plus gamma options. Numbers at nodes indicate bootstrap values Legend of Fig. 4: This legend is missing in Fig. 4. The correct legend should be read: Fig. 4 Phylogenetic tree of the hsp90 gene sequence dataset describing the evolutionary relationships within populations of Pratylenchus penetrans and other Pratylenchus species using Maximum Likelihood (ML) method. Branch lengths are proportional to the distances as derived from the distance matrix obtained using the GTR method with the invariant site plus gamma options. Numbers at nodes indicate bootstrap values Eur J Plant Pathol (2018) 152:573-574 https://doi.