Contribution of the Endoplasmic Reticulum to Peroxisome Formation

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2005.04.025 Byline: Dominic Hoepfner (1)(2), Danny Schildknegt (1), Ineke Braakman (1), Peter Philippsen (2), Henk F. Tabak (1)(3)(4) Abstract: How peroxisomes are formed in eukaryotic cells is unknown but important for insight into a variety of diseases. Both human and yeast cells lacking peroxisomes due to mutations in PEX3 or PEX19 genes regenerate the organelles upon reintroduction of the corresponding wild-type version. To evaluate how and from where new peroxisomes are formed, we followed the trafficking route of newly made YFP-tagged Pex3 and Pex19 proteins by real-time fluorescence microscopy in Saccharomyces cerevisiae. Remarkably, Pex3 (an integral membrane protein) could first be observed in the endoplasmic reticulum (ER), where it concentrates in foci that then bud off in a Pex19-dependent manner and mature into fully functional peroxisomes. Pex19 (a farnesylated, mostly cytosolic protein) enriches first at the Pex3 foci on the ER and then on the maturing peroxisomes. This trafficking route of Pex3-YFP is the same in wild-type cells. These results demonstrate that peroxisomes are generated from domains in the ER. Author Affiliation: (1) Department of Cellular Protein Chemistry, University of Utrecht, Padualaan 8, NL-3548 CH Utrecht, The Netherlands (2) Lehrstuhl fur Angewandte Mikrobiologie, Biozentrum, Universitat Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland (3) Laboratory of Cell Biology, University Medical Center Utrecht, Heidelberglaan 100, NL-3584 CX Utrecht, The Netherlands (4) Academic Biomedical Centre, University of Utrecht, Yalelaan 1, NL-3548 CL Utrecht, The Netherlands Article History: Received 13 December 2004; Revised 15 March 2005; Accepted 25 April 2005 Article Note: (miscellaneous) Published: July 14, 2005