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Originally published In Press as doi:10.1074/jbc.M909285199 on April 27, 2000

J. Biol. Chem., Vol. 275, Issue 26, 20168-20178, June 30, 2000
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Regulation of Peroxisome Size and Number by Fatty Acid beta -Oxidation in the Yeast Yarrowia lipolytica*

Jennifer J. SmithDagger , Trevor W. Brown, Gary A. Eitzen§, and Richard A. Rachubinski

From the Department of Cell Biology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada

The Yarrowia lipolytica MFE2 gene encodes peroxisomal beta -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-induced MFE2 deletion strain, mfe2-KO, are larger and more abundant than those of the wild-type strain. Under growth conditions not requiring peroxisomes, peroxisomes of mfe2-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 beta -oxidation enzymes than do wild-type cells. We also show that increasing the level of the beta -oxidation enzyme thiolase results in enlarged peroxisomes. Our results implicate peroxisomal beta -oxidation in the control of peroxisome size and number in yeast.

* This work was supported by a grant from the Medical Research Council of Canada (to R. A. R.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF198225, X80052, X57854, and M86456.

Dagger Recipient of a Medical Research Council of Canada Studentship.

§ Recipient of a Studentship from the Alberta Heritage Foundation for Medical Research.

A Medical Research Council of Canada Senior Scientist and an International Research Scholar of the Howard Hughes Medical Institute. To whom correspondence should be addressed: Dept. of Cell Biology, 5-14 Medical Sciences Bldg., University of Alberta, Edmonton, Alberta T6G 2H7, Canada. Tel.: 780-492-9868; Fax: 780-492-9278; E-mail: rick.rachubinski@ualberta.ca.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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