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Published 22 May 2006. doi:10.1083/jcb.200601036
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 173, Number 4, 521-532
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Article

 The origin and maintenance of mammalian peroxisomes involves a de novo PEX16-dependent pathway from the ER

Peter K. Kim1, Robert T. Mullen2, Uwe Schumann2, and Jennifer Lippincott-Schwartz1

1 Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
2 Department of Cellular and Molecular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada

Correspondence to Jennifer Lippincott-Schwartz: jlippin{at}helix.nih.gov

Peroxisomes are ubiquitous organelles that proliferate under different physiological conditions and can form de novo in cells that lack them. The endoplasmic reticulum (ER) has been shown to be the source of peroxisomes in yeast and plant cells. It remains unclear, however, whether the ER has a similar role in mammalian cells and whether peroxisome division or outgrowth from the ER maintains peroxisomes in growing cells. We use a new in cellula pulse-chase imaging protocol with photoactivatable GFP to investigate the mechanism underlying the biogenesis of mammalian peroxisomes. We provide direct evidence that peroxisomes can arise de novo from the ER in both normal and peroxisome-less mutant cells. We further show that PEX16 regulates this process by being cotranslationally inserted into the ER and serving to recruit other peroxisomal membrane proteins to membranes. Finally, we demonstrate that the increase in peroxisome number in growing wild-type cells results primarily from new peroxisomes derived from the ER rather than by division of preexisting peroxisomes.

U. Schumann's present address is Section of Molecular Biology, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093.

Abbreviations used in this paper: Cb5-glyc, cytochrome b5; FLIP, fluorescence loss in photobleaching; PAGFP, photoactivatable GFP; PBD, peroxisome biogenesis disorder; PMP, peroxisomal membrane protein; PPL, preprolactin; RFP, red fluorescent protein; ROI, region of interest.


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