Disease relevance of COX1

• Sequences that are capable of restoring mitochondrial targeting to a truncated yeast cytochrome c oxidase subunit IV presequence are encoded within the genome of Escherichia coli and within the gene for a higher eukaryotic cytosolic protein, mouse dihydrofolate reductase [1].

High impact information on COX1

• Group II introns al1 and al2 of the yeast mtDNA cox1 gene encode reverse transcriptase-like proteins that function in RNA splicing and may play a role in intron mobility and excision [2].
• One member of this intron class (aI5c in the gene for cytochrome c oxidase subunit I) is capable of self-splicing in vitro, giving correct exon-exon ligation and resulting in the appearance of both linear and lariat forms of the excised intron [3].
• This maturase is required to splice the fourth intron of this gene and to splice the fourth intron of the mitochondrial gene oxi3 encoding cytochrome oxidase subunit I. We have cloned the nuclear gene NAM2, which codes for two overlapping RNAs, 3.2 kb and 3.0 kb long, which are transcribed in the same direction but differ at their 5' ends [4].
• Two intron sequences in yeast mitochondrial COX1 gene: homology among URF-containing introns and strain-dependent variation in flanking exons [5].
• We have unambiguously assigned the alpha-event senDNA (the 2.6 kb monomer) to the oxi3 gene locus and the beta-event senDNA to the oxi2 gene locus [6].

Biological context of COX1

• Expression of the yeast mitochondrial genes COX1 and COX3, which encode subunits I and III of cytochrome oxidase, respectively, is controlled by a common nuclear-encoded trans-acting factor [7].
• Finally, one point mutation (R129D) did not abolish Nam1p binding, yet displayed an obvious COX1/CYTB transcript defect [8].
• Introns aI1 and aI2 found in the gene COX1 in yeast mitochondria encode reverse transcriptases which promote site-specific insertion of the intron into intronless alleles ('homing') [9].
• The mutant phenotype can be partially rescued by the presence in the same cell of wild-type mitochondrial DNA and a rho(-) deletion genome in which the 5'-UTR, first exon, and first intron of COX1 are fused to the fourth codon of ATP6 [10].
• We have established the DNA sequence of two cis-dominant mutations located in the fourth intron, a14, of the yeast mitochondrial gene oxi3 [11].

Anatomical context of COX1

• The synthesis of Cox1p and Cox3p in mutant mitochondria is normal whereas Cox2p is barely detected among labeled mitochondrial polypeptides [12].
• Assembly of the mitochondrial membrane system. Physical map of the Oxi3 locus of yeast mitochondrial DNA [13].
• Peptides with sequences based on the leader sequence of yeast cytochrome c oxidase subunit IV (pCOX IV-(1-25)) activate the electrophoretic uptake of K+ and other cations such as tetraethylammonium and lysine by rat liver mitochondria with EC50 = 11-15 microM [14].
• To investigate the interaction of the presequence of the precursor of yeast cytochrome C oxidase subunit IV (COX IV) with phospholipid membranes, a series of single- and double-cysteine-substituted peptide variants derived from the 25-residue NH2-terminal presequence has been synthesized and modified with nitroxide spin labels [15].

Associations of COX1 with chemical compounds

• In a paromomycin-resistant background, mss1 and mto1 mutants are inefficient in processing the mitochondrial COX1 transcript for subunit 1 of cytochrome oxidase [16].
• A nonreverting strain, which is respiratory deficient because of a deletion in the mitochondrial oxi3 gene, was bombarded with tungsten microprojectiles coated with DNA bearing sequences that could correct the oxi3 deletion [17].
• The oxi3 locus was dissected by mutagenesis of DS6 with ethidium bromide and selection of new clones having less complex genotypes [13].
• In the case of cytochrome c oxidase subunit V, correct NH2-terminal processing was also demonstrated with the purified matrix protease [18].
• These included the precursors of the yeast proteins cytochrome c oxidase subunit Va, the F1-ATPase beta subunit, mitochondrial malate dehydrogenase, and the ATP/ADP carrier [19].

Physical interactions of COX1

• The copper domain of Cox11 may be an important docking motif for Cox1 or a Cox1-associated protein [20].

Regulatory relationships of COX1

• Disruption of the yeast nuclear PET54 gene blocks excision of mitochondrial intron aI5 beta from pre-mRNA for cytochrome c oxidase subunit I [21].

Other interactions of COX1

• A quantitative RT-PCR assay was set up to compare levels of spliced COX1 mRNA present in three strains: a wild-type rho + strain; the rho-strain 7-49b-11, which retains the entire COX1 transcription unit; and a strain bearing a null mutation in the nuclear PET54 gene [22].
• In vitro RNA footprint and deletion experiments have been used to define the p40-binding site on the leaders of COX1 and ATP9 mRNAs [23].
• Mutants of Saccharomyces cerevisiae that lack a functional MSS51 gene are respiratory deficient due to the absence of cytochrome c oxidase subunit 1 (Cox1p) [24].
• In addition, the intron contains a nucleotide sequence in which 15 out of 18 nucleotides are identical with a sequence in the intron of COX4, the nuclear gene encoding cytochrome c oxidase subunit 4 [25].
• Deletion of the COX7 gene in Saccharomyces cerevisiae reveals a role for cytochrome c oxidase subunit VII in assembly of remaining subunits [26].

Analytical, diagnostic and therapeutic context of COX1

• We have searched for suppressors of mutations in the ribozyme-encoding sections of a group II intron, the first intron in the COX1 gene of Saccharomyces cerevisiae, which was independently subjected to in vitro site-directed mutagenesis [27].
• We used polymerase chain reaction (PCR) techniques to detect infrequent rearrangements in mtDNA and report here on duplicative IVS transposition, twintron formation (e.g. bI1 insertion into another bI1 intron), and IVS insertions at canonical 5' exon-intron borders in S. pombe (cob1-bI1) and in S. cerevisiae (cox1-aI1) [28].

References