Expression of PEX11β Mediates Peroxisome Proliferation in the Absence of Extracellular Stimuli

doi:10.1074/jbc.273.45.29607

Expression of PEX11β Mediates Peroxisome Proliferation in the Absence of Extracellular Stimuli*

From the ^‡Department of Biology, The Johns Hopkins University, Baltimore, Maryland 21218 and the Departments of ^§Biological Chemistry and Cell Biology and Anatomy, and ^¶Pediatrics and Molecular Biology and Genetics, and the ^‖Howard Hughes Medical Institutes, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Abstract

Mammalian cells typically contain hundreds of peroxisomes but can increase peroxisome abundance further in response to extracellular stimuli. We report here the identification and characterization of two novel human peroxisomal membrane proteins, PEX11α and PEX11β. Overexpression of the human PEX11β gene alone was sufficient to induce peroxisome proliferation, demonstrating that proliferation can occur in the absence of extracellular stimuli and may be mediated by a single gene. Time course studies indicated that PEX11β induces peroxisome proliferation through a multistep process involving peroxisome elongation and segregation of PEX11β from other peroxisomal membrane proteins, followed by peroxisome division. Overexpression of PEX11α also induced peroxisome proliferation but at a much lower frequency than PEX11β in our experimental system. The patterns ofPEX11α and PEX11β expression were examined in the rat, the animal in which peroxisome proliferation has been examined most extensively. Levels of PEX11β mRNA were similar in all tissues examined and were unaffected by peroxisome-proliferating agents. Conversely, PEX11α mRNA levels varied widely among different tissues, were highest in tissues that are sensitive to peroxisome-proliferating agents, and were induced more than 10-fold in response to the peroxisome proliferators clofibrate and di(2-ethylhexyl) phthalate. Taken together, these data implicate PEX11β in the constitutive control of peroxisome abundance and suggest that PEX11α may regulate peroxisome abundance in response to extracellular stimuli.

Footnotes

↵* This work was supported by Grant DK45787 from the National Institutes of Health (to S. J. G.).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 GenBank™/EMBL Data Bank with accession number(s) AF093668 (HsPEX11α), AF093670 (HsPEX11β), AF093669(MmPEX11α), and AF093671 (MmPEX11β).
↵** Investigator of the Howard Hughes Medical Institutes.
↵‡ To whom correspondence should be addressed: Dept. of Biological Chemistry, Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205. Tel.: 410-955-3085 Fax: 410-955-0215; E-mail:Stephen.Gould{at}qmail.bs.jhu.edu.
Abbreviations:

DEHP

di(2-ethylhexyl) phthalate

EST

expressed sequence tag(s)

DPBS

Dulbecco’s modified phosphate-buffered saline

PMP

peroxisomal membrane protein.
- Received May 27, 1998.
- Revision received August 4, 1998.
The American Society for Biochemistry and Molecular Biology, Inc.