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.
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.
Petruzzella
V
V
Unit of Molecular Medicine, Ospedale Pediatrico Bambino Gesù, Rome, Italy.
Tiranti
V
V
Fernandez
P
P
Ianna
P
P
Carrozzo
R
R
Zeviani
M
M
D019883:Alkyl and Aryl Transferases / Q000235:genetics; D000595:Amino Acid Sequence; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D003001:Cloning, Molecular; D000079922:Copper Transport Proteins; D045222:Electron Transport Chain Complex Proteins; D003576:Electron Transport Complex IV / Q000235:genetics* / Q000378:metabolism; D020224:Expressed Sequence Tags; D005347:Fibroblasts / Q000201:enzymology; D005816:Genetic Complementation Test; D006801:Humans; D007888:Leigh Disease / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D000637:Transaminases; D014157:Transcription Factors / Q000235:genetics*
C086106:COX11 protein, S cerevisiae; C484188:COX11 protein, human; C107633:COX15 protein, S cerevisiae; C100359:COX17 protein, S cerevisiae; C491006:COX17 protein, human; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; D045222:Electron Transport Chain Complex Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; C090858:OXA1 protein; D011506:Proteins; C489345:SCO1 protein, human; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C490115:COX10 protein, human; D003576:Electron Transport Complex IV; D019883:Alkyl and Aryl Transferases; C086105:COX10 protein, S cerevisiae; D000637:Transaminases; C108099:PET112 protein, S cerevisiae