Logo of yeastJournal's HomeManuscript SubmissionAims and ScopeAuthor GuidelinesEditorial BoardHome
Yeast. 2000; 17(3): 188–200.
PMCID: PMC2448379

Predicting the Function and Subcellular Location of Caenorhabditis Elegans Proteins Similar to Saccharomyces Cerevisiae β-Oxidation Enzymes


The role of peroxisomal processes in the maintenance of neurons has not been thoroughly investigated. We propose using Caenorhabditis elegans as a model organism for studying the molecular basis underlying neurodegeneration in certain human peroxisomal disorders, e.g. Zellweger syndrome, since the nematode neural network is well characterized and relatively simple in function. Here we have identified C. elegans PEX-5 (C34C6.6) representing the receptor for peroxisomal targeting signal type 1 (PTS1), defective in patients with such disorders. PEX-5 interacted strongly in a two-hybrid assay with Gal4p–SKL, and a screen using PEX-5 identified interaction partners that were predominantly terminated with PTS1 or its variants. A list of C. elegans proteins with similarities to well-characterized yeast β-oxidation enzymes was compiled by homology probing. The possible subcellular localization of these orthologues was predicted using an algorithm based on trafficking signals. Examining the C termini of selected nematode proteins for PTS1 function substantiated predictions made regarding the proteins' peroxisomal location. It is concluded that the eukaryotic PEX5-dependent route for importing PTS1-containing proteins into peroxisomes is conserved in nematodes. C. elegans might emerge as an attractive model system for studying the importance of peroxisomes and affiliated processes in neurodegeneration, and also for studying a β-oxidation process that is potentially compartmentalized in both mitochondria and peroxisomes.

Full Text

The Full Text of this article is available as a PDF (150K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997 Sep 1;25(17):3389–3402. [PMC free article] [PubMed]
  • Bartel P, Chien CT, Sternglanz R, Fields S. Elimination of false positives that arise in using the two-hybrid system. Biotechniques. 1993 Jun;14(6):920–924. [PubMed]
  • Bun-Ya M, Maebuchi M, Hashimoto T, Yokota S, Kamiryo T. A second isoform of 3-ketoacyl-CoA thiolase found in Caenorhabditis elegans, which is similar to sterol carrier protein x but lacks the sequence of sterol carrier protein 2. Eur J Biochem. 1997 Apr 15;245(2):252–259. [PubMed]
  • Chervitz SA, Aravind L, Sherlock G, Ball CA, Koonin EV, Dwight SS, Harris MA, Dolinski K, Mohr S, Smith T, et al. Comparison of the complete protein sets of worm and yeast: orthology and divergence. Science. 1998 Dec 11;282(5396):2022–2028. [PMC free article] [PubMed]
  • Chevray PM, Nathans D. Protein interaction cloning in yeast: identification of mammalian proteins that react with the leucine zipper of Jun. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5789–5793. [PMC free article] [PubMed]
  • De Duve C, Baudhuin P. Peroxisomes (microbodies and related particles). Physiol Rev. 1966 Apr;46(2):323–357. [PubMed]
  • Didion T, Roggenkamp R. Targeting signal of the peroxisomal catalase in the methylotrophic yeast Hansenula polymorpha. FEBS Lett. 1992 Jun 1;303(2-3):113–116. [PubMed]
  • Dmochowska A, Dignard D, Maleszka R, Thomas DY. Structure and transcriptional control of the Saccharomyces cerevisiae POX1 gene encoding acyl-coenzyme A oxidase. Gene. 1990 Apr 16;88(2):247–252. [PubMed]
  • Einerhand AW, Voorn-Brouwer TM, Erdmann R, Kunau WH, Tabak HF. Regulation of transcription of the gene coding for peroxisomal 3-oxoacyl-CoA thiolase of Saccharomyces cerevisiae. Eur J Biochem. 1991 Aug 15;200(1):113–122. [PubMed]
  • Elgersma Y, van Roermund CW, Wanders RJ, Tabak HF. Peroxisomal and mitochondrial carnitine acetyltransferases of Saccharomyces cerevisiae are encoded by a single gene. EMBO J. 1995 Jul 17;14(14):3472–3479. [PMC free article] [PubMed]
  • Filppula SA, Yagi AI, Kilpeläinen SH, Novikov D, FitzPatrick DR, Vihinen M, Valle D, Hiltunen JK. Delta3,5-delta2,4-dienoyl-CoA isomerase from rat liver. Molecular characterization. J Biol Chem. 1998 Jan 2;273(1):349–355. [PubMed]
  • Fransen M, Van Veldhoven PP, Subramani S. Identification of peroxisomal proteins by using M13 phage protein VI phage display: molecular evidence that mammalian peroxisomes contain a 2,4-dienoyl-CoA reductase. Biochem J. 1999 Jun 1;340(Pt 2):561–568. [PMC free article] [PubMed]
  • Gould SG, Keller GA, Subramani S. Identification of a peroxisomal targeting signal at the carboxy terminus of firefly luciferase. J Cell Biol. 1987 Dec;105(6 Pt 2):2923–2931. [PMC free article] [PubMed]
  • Gurvitz A, Wabnegger L, Yagi AI, Binder M, Hartig A, Ruis H, Hamilton B, Dawes IW, Hiltunen JK, Rottensteiner H. Function of human mitochondrial 2,4-dienoyl-CoA reductase and rat monofunctional Delta3-Delta2-enoyl-CoA isomerase in beta-oxidation of unsaturated fatty acids. Biochem J. 1999 Dec 15;344(Pt 3):903–914. [PMC free article] [PubMed]
  • Hakkola EH, Autio-Harmainen HI, Sormunen RT, Hassinen IE, Hiltunen JK. The known purified mammalian 2,4-dienoyl-CoA reductases are mitochondrial isoenzymes. J Histochem Cytochem. 1989 Dec;37(12):1863–1867. [PubMed]
  • Hakkola EH, Hiltunen JK. The existence of two mitochondrial isoforms of 2,4-dienoyl-CoA reductase in the rat. Eur J Biochem. 1993 Jul 1;215(1):199–204. [PubMed]
  • Igual JC, Matallaná E, Gonzalez-Bosch C, Franco L, Pérez-Ortin JE. A new glucose-repressible gene identified from the analysis of chromatin structure in deletion mutants of yeast SUC2 locus. Yeast. 1991 May-Jun;7(4):379–389. [PubMed]
  • Koivuranta KT, Hakkola EH, Hiltunen JK. Isolation and characterization of cDNA for human 120 kDa mitochondrial 2,4-dienoyl-coenzyme A reductase. Biochem J. 1994 Dec 15;304(Pt 3):787–792. [PMC free article] [PubMed]
  • Kragler F, Langeder A, Raupachova J, Binder M, Hartig A. Two independent peroxisomal targeting signals in catalase A of Saccharomyces cerevisiae. J Cell Biol. 1993 Feb;120(3):665–673. [PMC free article] [PubMed]
  • Maebuchi M, Togo SH, Yokota S, Ghenea S, Bun-Ya M, Kamiryo T, Kawahara A. Type-II 3-oxoacyl-CoA thiolase of the nematode Caenorhabditis elegans is located in peroxisomes, highly expressed during larval stages and induced by clofibrate. Eur J Biochem. 1999 Sep;264(2):509–515. [PubMed]
  • Marzioch M, Erdmann R, Veenhuis M, Kunau WH. PAS7 encodes a novel yeast member of the WD-40 protein family essential for import of 3-oxoacyl-CoA thiolase, a PTS2-containing protein, into peroxisomes. EMBO J. 1994 Oct 17;13(20):4908–4918. [PMC free article] [PubMed]
  • Palosaari PM, Hiltunen JK. Peroxisomal bifunctional protein from rat liver is a trifunctional enzyme possessing 2-enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and delta 3, delta 2-enoyl-CoA isomerase activities. J Biol Chem. 1990 Feb 15;265(5):2446–2449. [PubMed]
  • Rehling P, Marzioch M, Niesen F, Wittke E, Veenhuis M, Kunau WH. The import receptor for the peroxisomal targeting signal 2 (PTS2) in Saccharomyces cerevisiae is encoded by the PAS7 gene. EMBO J. 1996 Jun 17;15(12):2901–2913. [PMC free article] [PubMed]
  • Roe CR, Millington DS, Norwood DL, Kodo N, Sprecher H, Mohammed BS, Nada M, Schulz H, McVie R. 2,4-Dienoyl-coenzyme A reductase deficiency: a possible new disorder of fatty acid oxidation. J Clin Invest. 1990 May;85(5):1703–1707. [PMC free article] [PubMed]
  • Smeland TE, Nada M, Cuebas D, Schulz H. NADPH-dependent beta-oxidation of unsaturated fatty acids with double bonds extending from odd-numbered carbon atoms. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6673–6677. [PMC free article] [PubMed]
  • Sommer JM, Cheng QL, Keller GA, Wang CC. In vivo import of firefly luciferase into the glycosomes of Trypanosoma brucei and mutational analysis of the C-terminal targeting signal. Mol Biol Cell. 1992 Jul;3(7):749–759. [PMC free article] [PubMed]
  • Subramani S. Protein import into peroxisomes and biogenesis of the organelle. Annu Rev Cell Biol. 1993;9:445–478. [PubMed]
  • Subramani S. PEX genes on the rise. Nat Genet. 1997 Apr;15(4):331–333. [PubMed]
  • Taniguchi K, Nonami T, Nakao A, Harada A, Kurokawa T, Sugiyama S, Fujitsuka N, Shimomura Y, Hutson SM, Harris RA, et al. The valine catabolic pathway in human liver: effect of cirrhosis on enzyme activities. Hepatology. 1996 Dec;24(6):1395–1398. [PubMed]
  • Togo SH, Maebuchi M, Yokota S, Bun-Ya M, Kawahara A, Kamiryo T. Immunological detection of alkaline-diaminobenzidine-negativeperoxisomes of the nematode Caenorhabditis elegans purification and unique pH optima of peroxisomal catalase. Eur J Biochem. 2000 Mar;267(5):1307–1312. [PubMed]
  • Wang H, Le Dall MT, Waché Y, Laroche C, Belin JM, Nicaud JM. Cloning, sequencing, and characterization of five genes coding for acyl-CoA oxidase isozymes in the yeast Yarrowia lipolytica. Cell Biochem Biophys. 1999;31(2):165–174. [PubMed]
  • Yang M, Wu Z, Fields S. Protein-peptide interactions analyzed with the yeast two-hybrid system. Nucleic Acids Res. 1995 Apr 11;23(7):1152–1156. [PMC free article] [PubMed]

Articles from Yeast (Chichester, England) are provided here courtesy of Hindawi Publishing Corporation


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    NCBI Bookshelf books that cite the current articles.
  • Gene
    Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
  • GEO Profiles
    GEO Profiles
    Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
  • HomoloGene
    HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
  • MedGen
    Related information in MedGen
  • Pathways + GO
    Pathways + GO
    Pathways and biological systems (BioSystems) that cite the current articles. Citations are from the BioSystems source databases (KEGG and BioCyc).
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.
  • Taxonomy
    Taxonomy records associated with the current articles through taxonomic information on related molecular database records (Nucleotide, Protein, Gene, SNP, Structure).
  • Taxonomy Tree
    Taxonomy Tree

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...