Defective valyl-tRNA synthetase hampers the mitochondrial respiratory chain in Neurospora crassa

• Type: Article in International Scientific Journal
• Date: 2012

Authors

duarte, m (Author) Other; videira, a (Author) ICBAS

Journal

Title: Biochemical Journal

Vol. 448

Pages: 297-306

ISSN: 0264-6021

Publisher: PORTLAND PRESS LTD

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-002-2BW

DOI: 10.1042/BJ20120963

Abstract (EN): Respiratory chain deficiency can result from alterations in mitochondrial and/or cytosolic protein synthesis due to the dual genetic origin of mitochondrial oxidative phosphorylation. In the present paper we report a point mutation (D750G) in the bifunctional VARS (valyl-tRNA synthetase) 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 aa(3) 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 VARY(D-G) mutation does not affect overall cytosolic protein synthesis. Expression of the wild-type vars gene rescues all of the mutant phenotypes, indicating that the VARS(D-G) mutation is a loss-of-function mutation that results in a combined respiratory chain deficiency.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10