Disease relevance of PET9

• The gene encoding the ANT2 isoform was found specifically induced in Simian virus 40 (SV40)-transformed, tumoral and mtDNA lacking rho degrees cell lines [1].

High impact information on PET9

• Interestingly, ANT-2, a highly homologous protein could not lead to cell death, demonstrating the specificity of the signal for apoptosis induction [2].
• In order to study whether a dominant phenotype, as in humans, could be observed, the aac2 mutant alleles were also inserted in combination with the endogenous wild-type AAC2 gene [3].
• Mutations in AAC2, equivalent to human adPEO-associated ANT1 mutations, lead to defective oxidative phosphorylation in Saccharomyces cerevisiae and affect mitochondrial DNA stability [3].
• Gene fusions between the PET9 gene and the gene encoding beta-galactosidase (lacZ) were constructed to define the location of sequences necessary for the mitochondrial delivery of the ADP/ATP translocator protein in vivo [4].
• DNA sequence analysis of the PET9 gene showed that it encoded a protein of 309 amino acids which exhibited a high degree of homology with mitochondrial translocator proteins from other sources [4].

Biological context of PET9

• The expression of the reporter gene reveals that the AAC2 gene possesses a strong inducible promoter [5].
• The centromere linked pdr3-2 mutation exhibited also genetic linkage to pet9 with a map distance of 9.8 +/- 3.2 cM [6].
• The Klaac null mutation, which causes a respiratory-deficient phenotype, was fully complemented by AAC2, the Saccharomyces cerevisiae major gene for the ADP/ATP carrier and also by AAC1, a gene that is poorly expressed in S. cerevisiae [7].
• AAC2 contains a 954-base pair open reading frame coding for a protein of 318 amino acids which is highly homologous to the AAC1 gene product except that it is nine amino acids longer at the NH2 terminus [8].
• Indeed, when cloned into multicopy plasmid, AAC3 was able to replace the disrupted AAC2 in the JLY-73 strain [9].

Anatomical context of PET9

• Comparison to the homologous mutants of yeast AAC2 permits attribution of the roles of these residues more to ADP/ATP transport or to AAC import into mitochondria [10].
• Although the site-directed C73S mutation in the ADP/ATP carrier (AAC) AAC2 gene from Saccharomyces cerevisiae produced a glycerol-positive strain, indicating that the mutant AAC is active, on isolation and reconstitution in egg yolk phosphatidylcholine, the C73S AAC had no transport activity, whereas the wild-type AAC was fully active [11].

Associations of PET9 with chemical compounds

• A pet9 mutant which lacks a functional ADP-ATP translocator and is therefore respiration dependent was rapidly inhibited by polygodial [12].
• The UAS of the AAC2 gene is required for activation by HAP2 and heme and for release from glucose repressin [5].
• The gene encoding AAC2 was also cloned and sequenced from an op1 revertant capable of growth on glycerol as a sole carbon source [9].
• We have initiated this structure-function analysis by characterizing and confirming that the pet9 mutation is a G to A transition resulting in an arginine to histidine change at position 96 [13].
• Structure-function studies of adenine nucleotide transport in mitochondria. II. Biochemical analysis of distinct AAC1 and AAC2 proteins in yeast [14].

Regulatory relationships of PET9

• KlAAC was not subject to control by KlHap2, in contrast to AAC2 which is regulated by the Hap2 complex in S. cerevisiae [15].

Other interactions of PET9

• RPL19B is also closely linked to a mitochondrial ADP/ATP carrier protein gene AAC2 [16].
• Oxygen- and carbon source-dependent transactivation effect of ABF1 on the expression of the AAC2 gene encoding mitochondrial ADP/ATP carrier [17].
• Map positions of pet9, pep1 and pdr4 with respect to CEN2 [18].
• A recombinant fusion protein combining the mitochondrial ADP/ATP carrier (Anc2p) and the iso-1-cytochrome c (Cyc1p), both from Saccharomyces cerevisiae, has been genetically elaborated with the aim of increasing the polar surface area of the carrier to facilitate its crystallization [19].

Analytical, diagnostic and therapeutic context of PET9

• Titration of CATR and BA binding sites ended in the same number of sites, namely, 6-7 nmol/mg of wild-type and variant Anc2p [20].

References