Disease relevance of COX3

• In atp6 and cox3 from Russula rosacea, one of the outgroup taxa, we observed a number of in-frame TGA(trp) codons, which imply a Neurospora crassa-type mitochondrial code in R. rosacea and possibly in basidiomycetes in general [1].

High impact information on COX3

• 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 [2].
• Accumulation of mitochondrially synthesized Saccharomyces cerevisiae Cox2p and Cox3p depends on targeting information in untranslated portions of their mRNAs [3].
• In this study, we tested whether chimeric mRNAs with the untranslated sequences normally present on the mRNA encoding soluble Var1p, can direct functional expression of coding sequences specifying the integral membrane proteins Cox2p and Cox3p [3].
• Contrary to the belief that editing is absent from bryophytes, here we report mitochondrial RNA editing in cox3 mRNA of the liverwort Pellia epiphylla, the mosses Tetraphis pellucida and Ceratodon purpureus and the hornwort Anthroceros crispulus [4].
• Mitochondrial translation of the oxi2 mRNA, encoding yeast cytochrome c oxidase subunit III (coxIII), has previously been shown to specifically require the mitochondrially located protein product of the nuclear gene PET494 [5].

Biological context of COX3

• Two blocks of RNA sequence present in COX3 have similar counterparts within intron aI5 beta of COX1 [6].
• One such revertant carried a missense mutation in the PET122 gene that was a strong and dominant suppressor of the cold-sensitive defect in the mRNA, indicating that the PET122 protein interacts functionally (possibly directly) with the COX3 mRNA 5' leader [7].
• To bridge this gap a synthetic gene, ARG8m, designed to specify an arginine biosynthetic enzyme when expressed inside mitochondria, has been inserted into yeast mtDNA in place of the COX3 structural gene [8].
• This mitochondrial cox3::ARG8m gene fully complements a nuclear arg8 deletion at the level of cell growth, and it is dependent for expression upon nuclear genes that encode subunits of the COX3 mRNA-specific translational activator [8].
• 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 [9].

Anatomical context of COX3

• COX3 mRNA-specific translational activator proteins are associated with the inner mitochondrial membrane in Saccharomyces cerevisiae [10].
• We have previously observed that mutations which remove the carboxy-terminal region of PET122 block translation of the COX3 mRNA but can be suppressed by unlinked nuclear mutations in several genes, two of which have been shown to code for proteins of the small subunit of mitochondrial ribosomes [11].
• This decrease leads to low steady-state levels of Cox1p, Cox2p, and Cox3p, loss of visible spectra of aa(3) cytochromes, and low cytochrome c oxidase activity in mutant mitochondria [12].

Associations of COX3 with chemical compounds

• Importantly, transcript levels from the mitochondrial OLI1 gene, which has an associated organellar UAS, were attenuated in the DeltaYJR127C mutant during glycerol-based growth, but those from COX3 (OXI2), which lacks an associated mitochondrial UAS, were not [13].
• Analysis of mitochondrial RNA in cytoplasmic petite mutants containing the oxi2 gene, but with varying lengths of flanking sequences, suggest the presence of a common promoter for oxi2 and the upstream valine tRNA [14].
• A mitochondrial cox3 gene in the alkane yeast, Yarrowia lipolytica, encodes a subunit-3 protein of cytochrome c oxidase, and contains a 1044 base-pair-long intron, as compared with the corresponding intronless gene in Saccharomyces cerevisiae [15].

Regulatory relationships of COX3

• The data are consistent with models in which the PET494 protein acts within the mitochondria to specifically promote the translation of the oxi2 messenger RNA [16].

Other interactions of COX3

• The core of the cytochrome c oxidase complex is composed of its three largest subunits, Cox1p, Cox2p, and Cox3p, which are encoded in mitochondrial DNA of Saccharomyces cerevisiae and inserted into the inner membrane from the inside [17].
• Interestingly, the OXA1 gene, located on the yeast chromosome VIII, is adjacent to the gene PET 122, which controls the initiation of cox3 mRNA translation [18].
• Therefore, the PET122 gene product is a protein required for the expression of COX3 at some step after transcription and 5'-end processing of its transcript [19].
• Furthermore, a nonsense mutation introduced near the beginning of the PET54 open reading frame abolished both COX1 and COX3 gene expression [20].
• Two regions of the wild-type mtDNA (between cyb and oli2 and between SrRNA and oxi2) appear to be dispensable for mitochondrial function [21].

Analytical, diagnostic and therapeutic context of COX3

• Quantitation of relative fluorescence by flow cytometry confirmed that cox3 :: GFP(m)-3 expression was affected by carbon source and dependent upon COX3 mRNA-specific translational activation [22].
• Molecular cloning and nucleotide sequence of the nuclear PET122 gene required for expression of the mitochondrial COX3 gene in S. cerevisiae [23].
• Here, we confirm the proteolytic activity by site-directed mutagenesis and demonstrate that the proteins Cox1, Cox3, Cob, Su6, Su8 and Su9 are substrates of Afg3p [24].
• These sequences were used to design PCR primers for the amplification of partial atp6 and cox3 sequences from other members of the Boletales and outgroup taxa [1].

References