Neurospora strains harboring mitochondrial disease-associated mutations in iron-sulfur subunits of complex I

• Type: Article in International Scientific Journal
• Date: 2005

Authors

duarte, m (Author) ICBAS; schulte, u (Author) Other; ushakova, av (Author) Other; videira, a (Author) ICBAS

Journal

Title: Genetics

Vol. 171

Pages: 91-99

ISSN: 0016-6731

Publisher: Genetics Society of America

Indexing

ISI Web of Knowledge - 8 Citations

Scopus - 10 Citations

Other information

Authenticus ID: P-000-1JK

DOI: 10.1534/genetics.105.041517

Abstract (EN): We subjected the genes encoding the 19.3-, 21.3c-, and 51-kDa iron-sulfur subunits of respiratory chain complex I from Neurospora crassa to site-directed mutagenesis to mimic mutations in human complex I subunits associated with mitochondrial diseases. The V135M substitution was introduced into the 19.3-kDa cDNA, the P88L and R111H substitutions were separately introduced into the 21.3c-kDa cDNA, and the A353V and T435M alterations were separately introduced into the 51-kDa cDNA. The altered cDNAs were expressed in the corresponding null-mutants under the control of a heterologous promoter. With the exception of the A353V polypeptide, all mutated subunits were able to promote assembly of a functional complex I, rescuing the phenotypes of the respective null-mutants. Complex I from these strains displays spectroscopic and enzymatic properties similar to those observed in the wild-type strain. A decrease in total complex I amounts may be the major impact of the mutations, although expression levels of mutant genes from the heterologous promoter were sometimes lower and may also account for complex I levels. We discuss these findings in relation to the involvement of complex I deficiencies in mitochondrial disease.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9