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

doi:10.1006/geno.1998.5580

Genomics

Volume 54, Issue 3, 15 December 1998, Pages 494-504

https://doi.org/10.1006/geno.1998.5580 Get rights and content

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-coxidase. 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 anin vitroimport 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.

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^☆: Sequence data from this article have been deposited with the GenBank Data Library under Accession Nos. AF026849 (BCS1), AF026851 (PET112), AF026852 (SCO1), AF026850 (COX15.1), AF044323 (COX15.2 and COX15.3), AF044321 (COX11.1 and COX11.2), and AF044322 (ψ-COX11).

¹: To whom correspondence should be addressed at the Division of Biochemistry & Genetics, National Neurological Institute “C. Besta,” Via Celoria, 11, Milan 20133, Italy. Telephone: +39-2-2394388. Fax: +39-2-2664236. E-mail:[email protected].

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Regular ArticleIdentification 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☆

Abstract

FEBS Lett.

Gene

Gene

J. Biol. Chem.

J. Biol. Chem.

Biochim. Biophys. Acta.

Genomics

J. Biol. Chem.

Molecular analysis of cytochromec

Ann. Neurol.

Isolation of a cDNA encoding the human homolog of COX17, a yeast gene essential for mitochondrial copper recruitment

Hum. Genet.

Sequence and organization of the human mitochondrial genome

Nature

A panel of subchromosomal painting libraries covering over 300 regions of the human chromosome complement

Cytogenet. Cell. Genet.

Biogenesis of mitochondria

Annu. Rev. Cell. Biol.

Oxygen activation and the conservation of energy in cell respiration

Nature

Cloning of a human gene involved in cytochrome oxidase assembly by functional complementation of an oxa1−Saccharomyces cerevisiae.

Proc. Natl. Acad. Sci. USA

Immunological identification of yeastSCO1

Mol. Gen. Genet.

Cytochromec

Ann. Neurol.

The human mitochondrial transcription termination factor (mTERF) is a multizipper protein but binds to DNA as a monomer, with evidence pointing to intramolecular leucine zipper interactions

EMBO J.

Internal targeting signal of the BCS1 protein: A novel mechanism of import into mitochondria

EMBO J.

Isolation of a human cDNA for heme A:farnesyltransferase by functional complementation of a yeast cox10 mutant

Proc. Natl. Acad. Sci. USA

Regular Article
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☆

Cloning of a human gene involved in cytochrome oxidase assembly by functional complementation of an oxa1⁻Saccharomyces cerevisiae.