Identification and characterization of human cDNAs specific to BCS1, PET112, SCO1, COX15, and COX11, five genes involved in the formation and function of the mitochondrial respiratory chain.

TitleIdentification and characterization of human cDNAs specific to BCS1, PET112, SCO1, COX15, and COX11, five genes involved in the formation and function of the mitochondrial respiratory chain.
Publication TypeJournal Article
Year of Publication1998
AuthorsPetruzzella, V, Tiranti, V, Fernandez, P, Ianna, P, Carrozzo, R, Zeviani, M
JournalGenomics
Volume54
Issue3
Pagination494-504
Date Published1998 Dec 15
ISSN0888-7543
KeywordsAlkyl and Aryl Transferases, Amino Acid Sequence, Carrier Proteins, Cation Transport Proteins, Chromosome Mapping, Chromosomes, Human, Pair 17, Cloning, Molecular, Electron Transport Complex IV, Expressed Sequence Tags, Fibroblasts, Genetic Complementation Test, Humans, Leigh Disease, Membrane Proteins, Mitochondria, Mitochondrial Proteins, Molecular Chaperones, Molecular Sequence Data, Mutation, Nuclear Proteins, Proteins, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid, Tissue Distribution, Transaminases, Transcription Factors
Abstract

We have successfully applied a strategy based on the "cyberscreening" of the expressed sequence tags database using yeast protein sequences as "probes" to identify the human gene orthologs to BCS1, COX15, PET112, COX11, and SCO1, five yeast genes involved in the biogenesis of the mitochondrial respiratory chain complexes. In yeast, BCS1 is involved mainly in the assembly of complex III, while the other genes appear to control the structure/function of cytochrome-c oxidase. Significant amino acid identity and similarity were demonstrated by comparison of the human with the corresponding yeast polypeptides. Sequence alignment revealed numerous colinear identical regions and the conservation of functional domains. Mitochondrial targeting of the human gene products, suggested by computer analysis of the protein sequences, was confirmed by an in vitro import and protease-protection assay. These data strongly suggest that the human gene products share similar or identical functions with their yeast homologues. Genes controlling the structure/function of the respiratory chain complexes are attractive candidates for human mitochondrial disorders such as Leigh disease. However, both sequence analysis and functional complementation assays on an index patient do not support an etiological role for any of these genes.

DOI10.1006/geno.1998.5580
Alternate JournalGenomics
Citation Key10.1006/geno.1998.5580
PubMed ID9878253
Grant List767 / / Telethon / Italy