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J. Biol. Chem., Vol. 280, Issue 41, 34933-34939, October 14, 2005

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Pex3p Initiates the Formation of a Preperoxisomal Compartment from a Subdomain of the Endoplasmic Reticulum in Saccharomyces cerevisiae^*

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

Peroxisomes are dynamic organelles that often proliferate in response to compounds that they metabolize. Peroxisomes can proliferate by two apparent mechanisms, division of preexisting peroxisomes and de novo synthesis of peroxisomes. Evidence for de novo peroxisome synthesis comes from studies of cells lacking the peroxisomal integral membrane peroxin Pex3p. These cells lack peroxisomes, but peroxisomes can assemble upon reintroduction of Pex3p. The source of these peroxisomes has been the subject of debate. Here, we show that the amino-terminal 46 amino acids of Pex3p of Saccharomyces cerevisiae target to a subdomain of the endoplasmic reticulum and initiate the formation of a preperoxisomal compartment for de novo peroxisome synthesis. In vivo video microscopy showed that this preperoxisomal compartment can import both peroxisomal matrix and membrane proteins leading to the formation of bona fide peroxisomes through the continued activity of full-length Pex3p. Peroxisome formation from the preperoxisomal compartment depends on the activity of the genes PEX14 and PEX19, which are required for the targeting of peroxisomal matrix and membrane proteins, respectively. Our findings support a direct role for the endoplasmic reticulum in de novo peroxisome formation.

Received for publication, June 7, 2005 , and in revised form, August 5, 2005.

^* This work was supported in part by Grant MOP-15131 from the Canadian Institutes of Health Research (to R. A. R.) The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental videos 1 and 2.

¹ Recipient of a studentship from the Alberta Heritage Foundation for Medical Research.

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

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