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Molecular and Cellular Biology, December 2002, p. 8226-8240, Vol. 22, No. 23
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.23.8226-8240.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

PEX11{alpha} Is Required for Peroxisome Proliferation in Response to 4-Phenylbutyrate but Is Dispensable for Peroxisome Proliferator-Activated Receptor Alpha-Mediated Peroxisome Proliferation

Xiaoling Li,1 Eveline Baumgart,1 Gao-Xiang Dong,2 James C. Morrell,1 Gerardo Jimenez-Sanchez,3 David Valle,3 Kirby D. Smith,2 and Stephen J. Gould1*

Department of Biological Chemistry,1 Kennedy Krieger Institute and Department of Neurology,2 Howard Hughes Medical Institute and Departments of Pediatrics and of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 212053

Received 17 January 2002/ Returned for modification 18 March 2002/ Accepted 26 July 2002

The PEX11 peroxisomal membrane proteins promote peroxisome division in multiple eukaryotes. As part of our effort to understand the molecular and physiological functions of PEX11 proteins, we disrupted the mouse PEX11{alpha} gene. Overexpression of PEX11{alpha} is sufficient to promote peroxisome division, and a class of chemicals known as peroxisome proliferating agents (PPAs) induce the expression of PEX11{alpha} and promote peroxisome division. These observations led to the hypothesis that PPAs induce peroxisome abundance by enhancing PEX11{alpha} expression. The phenotypes of PEX11{alpha}-/- mice indicate that this hypothesis remains valid for a novel class of PPAs that act independently of peroxisome proliferator-activated receptor alpha (PPAR{alpha}) but is not valid for the classical PPAs that act as activators of PPAR{alpha}. Furthermore, we find that PEX11{alpha}-/- mice have normal peroxisome abundance and that cells lacking both PEX11{alpha} and PEX11ß, a second mammalian PEX11 gene, have no greater defect in peroxisome abundance than do cells lacking only PEX11ß. Finally, we report the identification of a third mammalian PEX11 gene, PEX11{gamma}, and show that it too encodes a peroxisomal protein.

* Corresponding author. Mailing address: Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 North Wolfe S., Baltimore, MD 21205. Phone: (410) 955-3424. Fax: (410) 955-0215. E-mail: sgould{at}jhmi.edu.

Molecular and Cellular Biology, December 2002, p. 8226-8240, Vol. 22, No. 23
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.23.8226-8240.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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