PMID:22957697

Citation	Duarte, M and Videira, A' (2012) Defective valyl tRNA synthetase hampers the mitochondrial respiratory chain in Neurospora crassa. Biochem. J. '
Abstract	Respiratory chain deficiency can result from alterations in mitochondrial and/or cytosolic protein synthesis due to the dual genetic origin of the mitochondrial oxidative phosphorylation. Herein, we report a point mutation (D750G) in the bifunctional valyl tRNA synthetase (VARS) of the fungus Neurospora crassa, associated with a temperature-sensitive phenotype. Analysis of the mutant strain revealed decreased steady-state levels of VARS and a clear reduction in the rate of mitochondrial protein synthesis. We observed a robust induction of the mitochondrial alternative oxidase with a concomitant decrease in the canonical respiratory pathway, namely in cytochrome b and aa3 content. Furthermore, the mutant strain accumulates the peripheral arm of complex I and depicts decreased levels of complexes III and IV consistent with severe impairment of the mitochondrial respiratory chain. The phenotypic alterations of the mutant strain are observed at the permissive growth temperature and exacerbated upon increase of the temperature. Surprisingly, glucose-6-phosphate dehydrogenase activities were similar in the wild type and mutant strains, whereas mitochondrial activities for succinate dehydrogenase and alternative NADH dehydrogenases were increased in the mutant strain, suggesting that the VARSD-G mutation does not affect overall cytosolic protein synthesis. Expression of wild type vars gene rescues all the mutant phenotypes indicating that the VARSD-G mutation is a loss of function mutation that results in a combined respiratory chain deficiency.
Links	PubMed Online version:10.1042/BJ20120963
Keywords
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
NEUCR:SYV		GO:0004832: valine-tRNA ligase activity	ECO:0000314:		F		Figure 6 shows altered mitochondrial proteins in vars mutants.	complete CACAO 5716
NEUCR:SYV		GO:0004812: aminoacyl-tRNA ligase activity	ECO:0000314:		F		Figure 5 shows altered cytochrome content due to vars mutation.	complete CACAO 5821

References

See Help:References for how to manage references in GONUTS.