Disease relevance of POX1

• The down-regulating effect of anoxia on the expression of CTA1 and POX1 is even stronger than the effect of haem deficiency and is not reversed by the addition of exogenous haem or the presence of endogenous haem [1].
• One of the acyl-CoA oxidases from the yeast Yarrowia lipolytica, acyl-CoA oxidase 2 (Aox2p), has been expressed in Escherichia coli as an active, N-terminally tagged (His)(6) fusion protein [2].

High impact information on POX1

• A significant redistribution of Aox occurs only in mature peroxisomes [3].
• Peroxisomal targeting of the Aox complex is abolished in a mutant lacking the peroxin Pex5p, a component of the matrix protein targeting machinery [4].
• Aox2p and Aox3p play a pivotal role in the formation of the Aox complex in the cytosol and can substitute for one another in promoting assembly of the complex [4].
• Peb1 is a peroxisome biogenesis mutant isolated in Saccharomyces cerevisiae that is selectively defective in the import of thiolase into peroxisomes but has a normal ability to package catalase, luciferase and acyl-CoA oxidase (Zhang, J. W., C. Luckey, and P. B. Lazarow. 1993. Mol. Biol. Cell. 4:1351-1359) [5].
• Cell-free mRNA translation and RNA dot-blot hybridization analyses demonstrated that, whereas glucose-grown C. tropicalis contained little or no acyl-CoA oxidase mRNA, alkane-grown cells contained so much of this mRNA as to make acyl-CoA oxidase one of the major in vitro translation products [6].

Biological context of POX1

• The POX1 promoter was shown to contain a canonical Adr1p element (UAS1), within which the oleate response element (ORE) was nested [7].
• Northern analysis demonstrated that transcriptional up-regulation of both POX1 and PEX11 was abolished in adr1 Delta mutant cells, and immunoblotting confirmed that the abundance of their gene products was dramatically reduced [7].
• Previously, we characterized regulatory elements in the promoter region of POX1 that are involved in the repression and activation of this gene (Wang, T., Luo, Y., and Small, G. M. (1994) J. Biol. Chem. 269, 24480-24485) [8].
• Transcription of POX1, the gene encoding peroxisomal acyl-CoA oxidase in the yeast Saccharomyces cerevisiae, is controlled by the carbon source given for cell growth [9].
• Elimination of this DNA sequence results in constitutive expression of POX1 when S. cerevisiae is grown on a fermentable carbon source or glycerol [10].

Anatomical context of POX1

• Saccharomyces cerevisiae Adr1p governs fatty acid beta-oxidation and peroxisome proliferation by regulating POX1 and PEX11 [7].
• To elucidate the molecular mechanism governing fatty acid transport across the cell membrane, we first isolated a Saccharomyces cerevisiae mutant, B-1, that exhibits a reduced acyl-CoA oxidase activity and an increase in free fatty acid accumulation [11].
• We have synthesized a 125I-peptide with the sequence of the last 12 amino acids of acyl-CoA oxidase, D-Tyr-HKHLKPLQSKL (SKLp), and used it to detect a receptor that recognizes SKL containing proteins targeted to glyoxysomes [12].
• However, there are also two sites on alkali-stripped glyoxysomal membranes from castor bean (Ricinus communis) endosperm that bind the peptide YHKHLKPLQSKL (SKLp), the sequence of the last 12 amino acids of acyl-coenzyme A oxidase (N.E. Wollins, R.P. Donaldson [1994] J Biol Chem 289: 1149-1153) [13].
• Under these conditions, catalase, acyl-coenzyme A oxidase, and malate synthase cofractionated at equilibrium close to the mitochondrial peak, indicating smaller, less dense organelles than those from cells grown on oleic acid [14].

Associations of POX1 with chemical compounds

• A screening strategy has been developed and used to identify eight S. cerevisiae mutants, from three complementation groups, that are defective in the oleate induction of POX1 [15].
• When cells are grown in the presence of glucose, the expression of POX1 mRNA is repressed, whereas growth on a carbon source such as glycerol or raffinose causes derepression [8].
• We evaluated acyl coenzyme A (acyl-CoA) oxidase activity (encoded by the POX1 through POX5 genes) in Yarrowia lipolytica in lactone accumulation and gamma-decalactone reconsumption in POX mutants [16].
• Cloning and characterization of the peroxisomal acyl CoA oxidase ACO3 gene from the alkane-utilizing yeast Yarrowia lipolytica [17].
• After centrifugation in a linear Ficoll gradient of the particulate fraction from the cells grown on ethanol and oleate the activity of acyl-CoA oxidase cosediments with catalase A. The relationship of catalase A to acyl-CoA oxidase is discussed [18].

Physical interactions of POX1

• Here we demonstrate that peroxisomal import of Pox1p is nevertheless dependent on binding to Pex5p, the PTS1 import receptor [19].

Regulatory relationships of POX1

• In this study we have purified and identified an oleate-activated transcription factor (Oaf1p) that binds to the activating sequence (UAS1) in the POX1 gene [8].
• POX1 has been shown to be transcriptionally activated in the presence of unsaturated fatty acids. frm2 was rescued by a region of DNA localized to chromosome III [20].

Other interactions of POX1

• Respiratory incompetence has no effect on the expression of CTA1 and POX1, whereas in the absence of haem their expression is markedly decreased [1].
• We recently identified and isolated a transcription factor, Oaf1p, that binds to the UAS1 of POX1 and mediates its induction [15].
• Here we demonstrate, using different techniques, that in Saccharomyces cerevisiae Pex5p-N alone facilitates the import of the major matrix protein Fox1p [21].
• Synthesis of polyhydroxyalkanoate was dependent on the beta-oxidation enzymes acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase multifunctional protein, which are involved in generating 3-hydroxyacyl-CoAs, and on the peroxin PEX5, which is involved in the import of proteins into the peroxisome [22].
• Mutants with no acyl-CoA oxidase activity could not reconsume gamma-decalactone, and mutants with a disruption of pox3, which encodes the short-chain acyl-CoA oxidase, reconsumed it more slowly [16].

Analytical, diagnostic and therapeutic context of POX1

• Among these clones, one containing a 1.7-kilobase insert coding for acyl-CoA oxidase (the first enzyme in the peroxisomal Beta-oxidation pathway) was identified by hybridization-selection translation and immunoprecipitation [6].
• Southern blot analysis revealed that POX2 had a significant homology to POX4, and also to gene POX5 which encodes a subunit (PXP-5) of the isozyme of acyl-CoA oxidase [23].
• We report the isolation and nucleotide (nt) sequence determination of a gene encoding peroxisomal fatty acyl-CoA oxidase (AOx) from the yeast Candida tropicalis pK233 [24].

References