Regulation of Peroxisome Size and Number by Fatty Acid β-Oxidation in the Yeast Yarrowia lipolytica

The Yarrowia lipolytica MFE2 gene encodes peroxisomal β-oxidation multifunctional enzyme type 2 (MFE2). MFE2 is peroxisomal in a wild-type strain but is cytosolic in a strain lacking the peroxisomal targeting signal-1 (PTS1) receptor. MFE2 has a PTS1, Ala-Lys-Leu, that is essential for targeting to peroxisomes. MFE2 lacking a PTS1 can apparently oligomerize with full-length MFE2 to enable targetting to peroxisomes. Peroxisomes of an oleic acid-inducedMFE2 deletion strain, mfe2-KO, are larger and more abundant than those of the wild-type strain. Under growth conditions not requiring peroxisomes, peroxisomes ofmfe2-KO are larger but less abundant than those of the wild-type strain, suggesting a role for MFE2 in the regulation of peroxisome size and number. A nonfunctional version of MFE2 did not restore normal peroxisome morphology to mfe2-KO cells, indicating that their phenotype is not due to the absence of MFE2.mfe2-KO cells contain higher amounts of β-oxidation enzymes than do wild-type cells. We also show that increasing the level of the β-oxidation enzyme thiolase results in enlarged peroxisomes. Our results implicate peroxisomal β-oxidation in the control of peroxisome size and number in yeast. The Yarrowia lipolytica MFE2 gene encodes peroxisomal β-oxidation multifunctional enzyme type 2 (MFE2). MFE2 is peroxisomal in a wild-type strain but is cytosolic in a strain lacking the peroxisomal targeting signal-1 (PTS1) receptor. MFE2 has a PTS1, Ala-Lys-Leu, that is essential for targeting to peroxisomes. MFE2 lacking a PTS1 can apparently oligomerize with full-length MFE2 to enable targetting to peroxisomes. Peroxisomes of an oleic acid-inducedMFE2 deletion strain, mfe2-KO, are larger and more abundant than those of the wild-type strain. Under growth conditions not requiring peroxisomes, peroxisomes ofmfe2-KO are larger but less abundant than those of the wild-type strain, suggesting a role for MFE2 in the regulation of peroxisome size and number. A nonfunctional version of MFE2 did not restore normal peroxisome morphology to mfe2-KO cells, indicating that their phenotype is not due to the absence of MFE2.mfe2-KO cells contain higher amounts of β-oxidation enzymes than do wild-type cells. We also show that increasing the level of the β-oxidation enzyme thiolase results in enlarged peroxisomes. Our results implicate peroxisomal β-oxidation in the control of peroxisome size and number in yeast. multifunctional enzyme type 2 open reading frame polymerase chain reaction peroxisomal targeting signal polyacrylamide gel electrophoresis base pair(s) Cellular fatty acid degradation into acetyl-CoA units occurs by β-oxidation, a cyclic reaction that shortens fatty acids by two carbon atoms per round. In higher eukaryotes, β-oxidation systems are found in both mitochondria and peroxisomes (reviewed in Ref. 1.Hashimoto T. Neurochem. Res. 1999; 24: 551-563Crossref PubMed Scopus (61) Google Scholar), whereas in lower eukaryotes such as yeast, this process occurs exclusively in peroxisomes (reviewed in Ref. 2.Endrizzi A. Pagot Y. Le Clainche A. Nicaud J.-M. Belin J.-M. Crit. Rev. Biotechnol. 1996; 16: 301-329Crossref PubMed Scopus (56) Google Scholar). The enzymes that contribute to β-oxidation in yeast include, in order, acyl-CoA oxidase, multifunctional enzyme type 2 (MFE2)1 (with 2-enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase activities) (3.Hiltunen J.K. Wenzel B. Beyer A. Erdmann R. Fosså A. Kunau W.-H. J. Biol. Chem. 1992; 267: 6646-6653Abstract Full Text PDF PubMed Google Scholar, 4.Qin Y.-M. Marttila M.S. Haapalainen A.M. Siivari K.M. Glumoff T. Hiltunen J.K. J. Biol. Chem. 1999; 274: 28619-28625Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar), and the cleavage enzyme, 3-ketoacyl-CoA thiolase. Peroxins are proteins that function in peroxisome assembly. Enzymes involved in peroxisomal β-oxidation are synthesized on free polysomes and then imported into the matrix of the peroxisome in an evolutionarily conserved manner that is dependent on a subset of peroxins and on cis-acting peroxisomal targeting signals (PTSs) (reviewed in Refs. 5.Subramani S. Physiol. Rev. 1998; 78: 171-188Crossref PubMed Scopus (284) Google Scholar and 6.Hettema E.H. Distel B. Tabak H.F. Biochim. Biophys. Acta. 1999; 1451: 17-34Crossref PubMed Scopus (106) Google Scholar). Proteins containing a PTS1 (a carboxyl-terminal tripeptide of the sequence SKL or a conserved variant thereof) require several peroxins for their import, including Pex5p, which binds directly to PTS1s. Proteins containing a PTS2, which has the consensus sequence (R/K)(L/V/I)X 5(Q/H)(L/A) and is found at or near the amino termini of a small subset of peroxisomal matrix proteins, also require several peroxins for their import, including Pex7p, which binds directly to PTS2s. An interesting feature of peroxisomes is their ability to import oligomeric proteins (7.Glover J.R. Andrews D.W. Rachubinski R.A. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 10541-10545Crossref PubMed Scopus (244) Google Scholar, 8.McNew J.A. Goodman J.M. J. Cell Biol. 1994; 127: 1245-1257Crossref PubMed Scopus (280) Google Scholar). 3-ketoacyl-CoA thiolase, the enzyme catalyzing the last step of peroxisomal β-oxidation, has been shown to be imported as a homodimer (7.Glover J.R. Andrews D.W. Rachubinski R.A. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 10541-10545Crossref PubMed Scopus (244) Google Scholar, 9.Titorenko V.I. Smith J.J. Szilard R.K. Rachubinski R.A. J. Cell Biol. 1998; 142: 403-420Crossref PubMed Scopus (106) Google Scholar). In many cell types, peroxisomes increase in size and number in response to certain extracellular stimuli (reviewed in Ref. 10.van den Bosch H. Schutgens R.B.H. Wanders R.J.A. Tager J.M. Annu. Rev. Biochem. 1992; 61: 157-197Crossref PubMed Scopus (737) Google Scholar). Evidence suggests that this regulation is controlled by a subset of peroxins. In yeast, Pex10p (11.Tan X. Waterham H.R. Veenhuis M. Cregg J.M. J. Cell Biol. 1995; 128: 307-319Crossref PubMed Scopus (119) Google Scholar), Pex11p (12.Erdmann R. Blobel G. J. Cell Biol. 1995; 128: 509-523Crossref PubMed Scopus (233) Google Scholar, 13.Marshall P.A. Krimkevich Y.I. Lark R.H. Dyer J.M. Veenhuis M. Goodman J.M. J. Cell Biol. 1995; 129: 345-355Crossref PubMed Scopus (174) Google Scholar, 14.Sakai Y. Marshall P.A. Saiganji A. Takabe K. Saiki H. Kato N. Goodman J.M. J. Bacteriol. 1995; 177: 6773-6781Crossref PubMed Google Scholar, 15.Marshall P.A. Dyer J.M. Quick M.E. Goodman J.M. J. Cell Biol. 1996; 135: 123-136Crossref PubMed Scopus (91) Google Scholar), and Pex16p (16.Eitzen G.A. Szilard R.K. Rachubinski R.A. J. Cell Biol. 1997; 137: 1265-1278Crossref PubMed Scopus (110) Google Scholar) have each been shown to play a role in regulating the size and/or number of peroxisomes in response to growth on carbon sources metabolized by peroxisomes. In mammalian cells, PEX11β has been shown to induce peroxisome proliferation in the absence of an external stimulus (e.g. a hypolipidemic drug such as clofibrate) (17.Schrader M. Reuber B.E. Morrell J.C. Jimenez-Sanchez G. Obie C. Stroh T.A. Valle D. Schroer T.A. Gould S.J. J. Biol. Chem. 1998; 273: 29607-29614Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar). Other evidence suggests that there is also metabolic control of peroxisome abundance and size in mammalian cells. Cells of a patient with a specific deficiency in acyl-CoA oxidase were shown to have enlarged peroxisomes that are heterogeneous in size (18.Poll-The B.T. Roels F. Ogier H. Scotto J. Vamecq J. Schutgens R.B.H. Wanders R.J.A. van Roermund C.W.T. van Wijland M.J.A. Schram A.W. Tager J.M. Saudubray J.-M. Am. J. Hum. Genet. 1988; 42: 422-434PubMed Google Scholar). It has also been reported that cells lacking acyl-CoA oxidase or MFE2 have a in peroxisome abundance and a increase in peroxisome as with normal cells S. D. J. Gould S.J. J. Cell Sci. 1999; PubMed Google Scholar). the and of gene of the yeast Yarrowia lipolytica and the of the targeting of to peroxisomes. We also evidence of a role for β-oxidation enzymes in the regulation of peroxisome size and number in Y. the evidence for this type of metabolic control in yeast. The yeast in this are in were as yeast yeast yeast oleic yeast base amino yeast base amino oleic yeast base amino and and were with the amino acids or were with and each at as at lipolytica in this in a A of gene the of lipolytica strain containing a (16.Eitzen G.A. Szilard R.K. Rachubinski R.A. J. Cell Biol. 1997; 137: 1265-1278Crossref PubMed Scopus (110) Google Scholar) into strain to oleic acid as a carbon A containing the and this strain and into to the a of gene is the of the the the MFE2 lipolytica the wild-type strain with and by polymerase chain reaction of each and that of containing the MFE2 gene were and in of this size into to a for A of the MFE2 gene by and with and to this a and both of the were The sequence of the MFE2 the gene sequence and with the by the of the for in this are by are in in a are by are in an MFE2 with and the containing the open reading frame of the MFE2 as as and of sequence and of the into the lipolytica A.M. C. G.A. J.R. Rachubinski R.A. Scopus Google Scholar) with to the the Y. lipolytica gene for the of yeast and the Y. lipolytica gene for lipolytica cells. The of the MFE2 were and for the and and for the The two were as for a of and and and the of a containing by a with and the into the of The Y. lipolytica gene by then into the to the The gene by and and with and the into the wild-type strain by that to and that were to on oleic acid were by strain, mfe2-KO, to have the MFE2 by The strain, as R.K. V.I. Veenhuis M. Rachubinski R.A. J. Cell Biol. 1995; PubMed Scopus Google Scholar), that the gene in of the A gene for a MFE2 at amino by a of the (a of of of at the of a the of the MFE2 gene the of the MFE2 gene the were and for the and and for the The two were as for a of with and and have and the of a containing both of gene with a with and and the containing the into the of A termini the which of the P.A. R.A. PubMed Scopus Google Scholar), with the of polymerase and into the to the and the containing the as as and of sequence and of the MFE2 into to the The of that by the and to be by A to a lacking carboxyl-terminal tripeptide of the MFE2 gene to the the carboxyl-terminal tripeptide of MFE2 with and The and sequence of MFE2 were with and The two were as for a of with and and have the of a containing a MFE2 gene with and the containing the MFE2 as as and of sequence and of the MFE2 into the of The sequence of the with the of to The of the MFE2 gene to be by Cells were in for 2 or as and for as J.R. PubMed Scopus Google Scholar), that in of for at with were a cells were in for at by in increasing of and in were an and in a were enlarged to a on of cells were and and the cell of of of peroxisome the peroxisome peroxisome were and and the peroxisome and by the number of peroxisomes peroxisome the of peroxisomes of peroxisomes per of cell by the of and and of Scholar) for as the number of peroxisome and reported as the number of peroxisomes per cell the peroxisome for each strain peroxisome cell the and the of peroxisomes and of Scholar). A to a MFE2 gene a version of MFE2 containing the and A of the MFE2 gene to the with and A of the MFE2 gene to the with and The two were as for a of with and and contain the and have the of a containing a MFE2 gene containing the A MFE2 with the the that and the and the were in of and The containing with and and into the of to the the containing the and with and into the of to with and the containing the as as and of sequence and of the MFE2 into the of to An containing the and of the gene Y. lipolytica a of the Y. lipolytica with and of the with and The two were as for a of with and and have and contain consensus the of a containing the and of the gene by a with and the into the of to the The gene lipolytica and with the of polymerase and into the of in the to the thiolase cells with or were in Cells were and were amounts of each strain at were by gel electrophoresis to and with or The in the of thiolase in the strain the wild-type strain by a of the for thiolase of of each strain. to Y. lipolytica thiolase and to Y. lipolytica have been G.A. V.I. Smith J.J. Veenhuis M. Szilard R.K. Rachubinski R.A. J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). The a acid of the to Y. lipolytica have been V.I. Rachubinski R.A. Biol. 1997; PubMed Scopus Google Scholar). to Y. oxidase were a of Nicaud and have been Le Y. C. Belin J.-M. C. Nicaud J.-M. J. Bacteriol. 1999; PubMed Google Scholar). to were a of of and Cell to Y. lipolytica Pex16p have been (16.Eitzen G.A. Szilard R.K. Rachubinski R.A. J. Cell Biol. 1997; 137: 1265-1278Crossref PubMed Scopus (110) Google Scholar). to Y. lipolytica were a of of Cell of were synthesized on an with an were the of of yeast by with growth of and of and were as R. Smith J.A. K. in Scholar). were a as PubMed Scopus Google Scholar). Proteins were to for a Biochem. PubMed Scopus Google Scholar), and were by of a a Y. lipolytica strain that an and that to on oleic to the of a of the MFE2 gene peroxisomal β-oxidation MFE2 sequence to a to the Y. lipolytica MFE2 gene by were of and the each were shown to be by that the the as as and and of the The Y. lipolytica MFE2 gene and are shown in A is found and is the of the of are found at and of the a feature to of Y. lipolytica G. C. Rev. 1997; PubMed Google Scholar). The of the MFE2 gene the sequence and sequence the consensus oleic of J.A. Rachubinski R.A. PubMed Scopus Google Scholar) and the consensus oleic M. B. H. PubMed Scopus Google Scholar, Biol. 1998; PubMed Scopus Google Scholar), which are found of peroxisomal matrix gene an Y. and G. C. Rev. 1997; PubMed Google Scholar) were and and and The the consensus whereas the sequence the consensus The S. consensus sequence of F. Full Text PDF PubMed Scopus Google Scholar) is also a feature of Y. lipolytica G. C. 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The are with the carboxyl-terminal tripeptide of MFE2 as a this tripeptide is a PTS1, a MFE2 gene a version of into both the mfe2-KO and wild-type The MFE2 gene to growth of mfe2-KO cells on oleic the of in both In mfe2-KO cells, the a cytosolic whereas thiolase a of peroxisomes that the carboxyl-terminal of MFE2 is a PTS1, as is essential for the targeting of to peroxisomes. the of in wild-type cells. a cytosolic in mfe2-KO cells, a of in wild-type cells that to the of peroxisomal thiolase results are with the import of MFE2 as an into peroxisomes. In a manner to has been shown for the import of the thiolase in S. (7.Glover J.R. Andrews D.W. Rachubinski R.A. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 10541-10545Crossref PubMed Scopus (244) Google Scholar), the of lacking PTS1 with full-length MFE2 in the and then be to the peroxisome by of the PTS1 of the full-length is Y. lipolytica MFE2 an is to that MFE2 of S. been shown to (3.Hiltunen J.K. Wenzel B. Beyer A. Erdmann R. Fosså A. Kunau W.-H. J. Biol. Chem. 1992; 267: 6646-6653Abstract Full Text PDF PubMed Google Scholar). evidence has that MFE2 has a role in peroxisome abundance and size S. D. J. Gould S.J. J. Cell Sci. 1999; PubMed Google Scholar). We the of the Y. lipolytica MFE2 gene on peroxisome that the peroxisomes ofmfe2-KO cells more in size and more abundant than peroxisomes of wild-type cells the peroxisomes of the strain were whereas the peroxisomes of the wild-type strain were and of Scholar) that mfe2-KO cells a of peroxisomes that that of wild-type cells and Peroxisomes of the mfe2-KO strain were also more in size than those of wild-type cells, with cells many peroxisomes than in and wild-type cells peroxisomes than in In the of larger than the peroxisomes and the for the peroxisome of mfe2-KO cells found to be larger than that of wild-type cells, with a and of peroxisomes in and of peroxisomes per of cell on of peroxisomes of peroxisomes per of cell of peroxisomes on not as peroxisomes were not not as peroxisomes were not not as peroxisomes were not not as peroxisomes were not not as peroxisomes were not not as peroxisomes were not not as peroxisomes were not of peroxisomes per of cell on of peroxisomes per of cell and of on not as peroxisomes were not in a The that peroxisomes are more abundant in the than in the wild-type strain not and can be by the that peroxisomes of the deletion strain are and a of peroxisomes can as peroxisome in Y. J. Cell Biol. PubMed Scopus Google Scholar). Our of oleic mfe2-KO cells a of peroxisome size and number in the absence of the for this the morphology of mfe2-KO cells in containing a carbon not requiring β-oxidation for Peroxisomes of in were larger than those of wild-type cells in of that the of peroxisomes of mfe2-KO cells that of wild-type cells, whereas the number of peroxisomes per of cell for both and a peroxisome not that the number of peroxisomes per cell is the for both the larger a peroxisome the the of in and of Scholar). the peroxisome number for cells of each strain, the peroxisome a that into peroxisome size and of Scholar). that in to for cells in oleic mfe2-KO cells as many peroxisomes as did wild-type cells growth in the enlarged peroxisomes cells were by the absence of MFE2 or the of a β-oxidation a nonfunctional version of the of the mfe2-KO strain. S. MFE2 has two dehydrogenase and in that are for the β-oxidation of fatty acids Y.-M. Marttila M.S. Haapalainen A.M. Siivari K.M. Glumoff T. Hiltunen J.K. J. Biol. Chem. 1999; 274: 28619-28625Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar). A of MFE2 containing the and in the of the two dehydrogenase has been shown to be nonfunctional in peroxisomal β-oxidation Y.-M. Marttila M.S. Haapalainen A.M. Siivari K.M. Glumoff T. Hiltunen J.K. J. Biol. Chem. 1999; 274: 28619-28625Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar). We two consensus in Y. lipolytica and of the S. and Y. lipolytica that and of Y. lipolytica MFE2 to and of S. The which the and and into mfe2-KO cells. The mfe2-KO strain with the mfe2-KO strain with the to on containing oleic acid as the carbon whereas the mfe2-KO strain with a on this on containing as the carbon and were by of yeast with The of and were in the yeast in which were The of the were in the of that amounts of were is to restore fatty acid β-oxidation to strain. on strain with strain with the peroxisomes larger than those of the mfe2-KO strain with which encodes a version of MFE2 The of peroxisomes for each strain Peroxisomes of the mfe2-KO strain were larger than peroxisomes of the wild-type strain, but not as as peroxisomes of the strain. the normal of a nonfunctional of enlarged peroxisomes, the of enlarged peroxisomes in the mfe2-KO strain not the of the absence of MFE2 An of the of several peroxisomal proteins in cell of the and wild-type in oleic or that two peroxisomal β-oxidation thiolase and acyl-CoA oxidase of Y. lipolytica acyl-CoA oxidase Le Y. C. Belin J.-M. C. Nicaud J.-M. J. Bacteriol. 1999; PubMed Google were in mfe2-KO cells as with wild-type cells by growth in each carbon The of two peroxisomal enzymes of the and the in wild-type cells or were in mfe2-KO cells. The of two peroxins that with the peroxisome Pex16p and were not in mfe2-KO cells with wild-type cells, and in both peroxins less abundant in the deletion strain than in the wild-type strain growth in oleic The of the were in of each strain growth that amounts of were It been shown that amounts of peroxisomal matrix proteins to enlarged peroxisomes in cells of S. and the yeast B. van Veenhuis M. Tabak H.F. J. Cell Biol. 1988; PubMed Scopus Google Scholar, A. Veenhuis M. R. Genet. 16: PubMed Scopus Google Scholar, R. T. Biol. PubMed Scopus Google Scholar). We amounts of peroxisomal β-oxidation enzymes contribute to peroxisome in Y. lipolytica cells. We the gene peroxisomal thiolase, in wild-type cells and the of this on peroxisome We at peroxisome size growth of cells in the level of thiolase is this a increase in the abundance of thiolase can be by of gene in wild-type cells in peroxisomes are small in cells in small in peroxisome size be growth in wild-type cells with more thiolase than did wild-type cells with the increase in the of thiolase to peroxisomes in the strain that were larger than those of the strain The and the of peroxisomes for each strain and Peroxisomes of the strain were as as peroxisomes of the wild-type strain, whereas the of peroxisomes for both results that an increase in abundance of peroxisomal β-oxidation enzymes in strain to the enlarged peroxisomes in this strain. The MFE2 gene of Y. lipolytica encodes peroxisomal which a of sequence with MFE2 proteins Y. lipolytica cells of MFE2 are to oleic acid as a carbon as has been for S. Y.-M. Marttila M.S. Haapalainen A.M. Siivari K.M. Glumoff T. Hiltunen J.K. J. Biol. Chem. 1999; 274: 28619-28625Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar). The Y. lipolytica MFE2 gene a oleic as do the of S. M. B. H. PubMed Scopus Google Scholar, Biol. 1998; PubMed Scopus Google Scholar) J.A. Rachubinski R.A. PubMed Scopus Google Scholar), and with the of a version of the by growth of Y. lipolytica on oleic lipolytica MFE2 a PTS1, as do the MFE2 proteins of C. and S. and is essential for targeting to peroxisomes. to S. which has been shown to (3.Hiltunen J.K. Wenzel B. Beyer A. Erdmann R. Fosså A. Kunau W.-H. J. Biol. Chem. 1992; 267: 6646-6653Abstract Full Text PDF PubMed Google Scholar), evidence suggests that Y. lipolytica MFE2 is to peroxisomes as an Y. lipolytica MFE2 to have a role in peroxisome Cells of the deletion strain mfe2-KO in oleic acid contain more and larger peroxisomes than do wild-type cells the peroxisomes of strain are more heterogeneous in size than those of wild-type cells and are found in to cells in a carbon not requiring peroxisomes for have larger peroxisomes than do wild-type cells, but as that MFE2 to the regulation of peroxisome size and number. mfe2-KO cells contain enlarged peroxisomes in the of both oleic acid and carbon with in yeast, peroxisomes are enlarged in a mammalian cell lacking MFE2 S. D. J. Gould S.J. J. Cell Sci. 1999; PubMed Google Scholar). The larger size of be the of amounts of peroxisomal β-oxidation enzymes in this strain. It has been shown that of matrix enzymes in cells of H. and S. to enlarged peroxisomes B. van Veenhuis M. Tabak H.F. J. Cell Biol. 1988; PubMed Scopus Google Scholar, A. Veenhuis M. R. Genet. 16: PubMed Scopus Google Scholar, R. T. Biol. PubMed Scopus Google Scholar). show that increasing the of thiolase in Y. lipolytica cells to enlarged peroxisomes, indicating that of β-oxidation proteins in mfe2-KO cells contribute to the enlarged peroxisomes in this strain, of and in peroxisomes in the mfe2-KO strain to mfe2-KO strain with the and have shown that the increase in peroxisome size for mfe2-KO cells is not due to the absence of MFE2 as a nonfunctional of MFE2 at normal MFE2 is to this that the of MFE2 to function in fatty acid β-oxidation to enlarged peroxisomes. of the MFE2 gene peroxisome number. growth in oleic mfe2-KO cells have more peroxisomes than do wild-type cells. In in have peroxisomes than do wild-type cells. A for this is that the number of peroxisomes a cell be by the of cell It has been that the number of peroxisomes in a cell is the of both peroxisome due to proliferation and peroxisome due to cell M. Goodman J.M. J. Cell Sci. PubMed Google Scholar). In to wild-type cells, cells of deletion strain in oleic of their peroxisomes to cells. peroxisomes to cells in the absence of cell of the of the strain to oleic peroxisomes in cells of the increasing the number of peroxisomes per with this is the that in cells at the of wild-type cells and do not have more peroxisomes than do wild-type cells. An for the number of peroxisomes in the oleic mfe2-KO cells is that of gene an of peroxisome proliferation this is not deletion of the the number of peroxisomes in Y. due to a of cell or a of peroxisome It be that peroxisomes in the are more abundant or as abundant peroxisomes of the wild-type strain on the growth S. D. J. Gould S.J. J. Cell Sci. 1999; PubMed Google Scholar) that peroxisomes are less abundant in cells lacking MFE2 than in normal cells. for the yeast and cells be the of in that the peroxisomes were peroxisomes in the cells are as are in oleic cells, the number of peroxisomes have been by this in peroxisome number yeast and cells a in the regulating peroxisome abundance in two be at the and involved in We for with

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