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Peroxisome synthesis in the absence of preexisting peroxisomes.

South ST, Gould SJ - J. Cell Biol. (1999)

Bottom Line: We also identified human PEX16, a novel integral peroxisomal membrane protein, and found that PBD061 had inactivating mutations in the PEX16 gene.These results demonstrate that peroxisomes do not necessarily arise from division of preexisting peroxisomes.We propose that peroxisomes may form by either of two pathways: one that involves PEX11-mediated division of preexisting peroxisomes, and another that involves PEX16-mediated formation of peroxisomes in the absence of preexisting peroxisomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

ABSTRACT
Zellweger syndrome and related diseases are caused by defective import of peroxisomal matrix proteins. In all previously reported Zellweger syndrome cell lines the defect could be assigned to the matrix protein import pathway since peroxisome membranes were present, and import of integral peroxisomal membrane proteins was normal. However, we report here a Zellweger syndrome patient (PBD061) with an unusual cellular phenotype, an inability to import peroxisomal membrane proteins. We also identified human PEX16, a novel integral peroxisomal membrane protein, and found that PBD061 had inactivating mutations in the PEX16 gene. Previous studies have suggested that peroxisomes arise from preexisting peroxisomes but we find that expression of PEX16 restores the formation of new peroxisomes in PBD061 cells. Peroxisome synthesis and peroxisomal membrane protein import could be detected within 2-3 h of PEX16 injection and was followed by matrix protein import. These results demonstrate that peroxisomes do not necessarily arise from division of preexisting peroxisomes. We propose that peroxisomes may form by either of two pathways: one that involves PEX11-mediated division of preexisting peroxisomes, and another that involves PEX16-mediated formation of peroxisomes in the absence of preexisting peroxisomes.

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A model of peroxisome biogenesis in the absence  (top) and presence (bottom) of  preexisting peroxisomes. During  rescue of PBD061 cells, PEX16  creates nascent peroxisomes, possibly from a preperoxisomal vesicle. These nascent PEX16-containing peroxisomes then import  additional PMPs. The import of  PEX11 proteins allows these  structures to proliferate by fission or by budding, and the import of other peroxins leads to  formation of a functional matrix  protein import apparatus. Under normal conditions, peroxisomes would form primarily  from preexisting peroxisomes in  a PEX11-mediated process. Although the targeting of PEX16 to  preperoxisomal structures may  be enhanced in the absence of  peroxisomal membranes, such a  process may also occur under  normal conditions.
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Figure 11: A model of peroxisome biogenesis in the absence (top) and presence (bottom) of preexisting peroxisomes. During rescue of PBD061 cells, PEX16 creates nascent peroxisomes, possibly from a preperoxisomal vesicle. These nascent PEX16-containing peroxisomes then import additional PMPs. The import of PEX11 proteins allows these structures to proliferate by fission or by budding, and the import of other peroxins leads to formation of a functional matrix protein import apparatus. Under normal conditions, peroxisomes would form primarily from preexisting peroxisomes in a PEX11-mediated process. Although the targeting of PEX16 to preperoxisomal structures may be enhanced in the absence of peroxisomal membranes, such a process may also occur under normal conditions.

Mentions: These and other lines of evidence suggested instead that peroxisome formation may occur by two distinct, yet overlapping pathways (Fig. 11). In this model, peroxisomes would typically form by division of preexisting peroxisomes in a process mediated by PEX11α and PEX11β, not PEX16. This would explain the hyperabundance of peroxisomes in cells overexpressing PEX11α or PEX11β, and the fact that overexpression of PEX16 does not induce any detectable proliferation of peroxisomes. In this model, PEX16 would function normally in importing PMPs into preexisting peroxisomes, and would itself be imported into preexisting peroxisomes. In the absence of PEX16, PMP import would cease, peroxisomes could not divide, and the organelle would eventually be lost from the cell population. In addition to this common route of peroxisome formation we propose that PEX16 may, at low efficiency, be targeted to an unknown preperoxisomal structure. The incorporation of PEX16 into such vesicles may convert them to nascent peroxisomes that are able to import other PMPs, and eventually to mature peroxisomes. This model would not only explain the ability of PEX16 to rescue PBD061 cells but would also explain: the presence of a few, large peroxisomes in mutants lacking the PEX11 gene (Erdmann and Blobel, 1995; Marshall et al., 1995); the peroxisome proliferation promoting activity of PEX11 proteins; and the lack of peroxisome proliferation promoting activity for PEX16.


Peroxisome synthesis in the absence of preexisting peroxisomes.

South ST, Gould SJ - J. Cell Biol. (1999)

A model of peroxisome biogenesis in the absence  (top) and presence (bottom) of  preexisting peroxisomes. During  rescue of PBD061 cells, PEX16  creates nascent peroxisomes, possibly from a preperoxisomal vesicle. These nascent PEX16-containing peroxisomes then import  additional PMPs. The import of  PEX11 proteins allows these  structures to proliferate by fission or by budding, and the import of other peroxins leads to  formation of a functional matrix  protein import apparatus. Under normal conditions, peroxisomes would form primarily  from preexisting peroxisomes in  a PEX11-mediated process. Although the targeting of PEX16 to  preperoxisomal structures may  be enhanced in the absence of  peroxisomal membranes, such a  process may also occur under  normal conditions.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2132891&req=5

Figure 11: A model of peroxisome biogenesis in the absence (top) and presence (bottom) of preexisting peroxisomes. During rescue of PBD061 cells, PEX16 creates nascent peroxisomes, possibly from a preperoxisomal vesicle. These nascent PEX16-containing peroxisomes then import additional PMPs. The import of PEX11 proteins allows these structures to proliferate by fission or by budding, and the import of other peroxins leads to formation of a functional matrix protein import apparatus. Under normal conditions, peroxisomes would form primarily from preexisting peroxisomes in a PEX11-mediated process. Although the targeting of PEX16 to preperoxisomal structures may be enhanced in the absence of peroxisomal membranes, such a process may also occur under normal conditions.
Mentions: These and other lines of evidence suggested instead that peroxisome formation may occur by two distinct, yet overlapping pathways (Fig. 11). In this model, peroxisomes would typically form by division of preexisting peroxisomes in a process mediated by PEX11α and PEX11β, not PEX16. This would explain the hyperabundance of peroxisomes in cells overexpressing PEX11α or PEX11β, and the fact that overexpression of PEX16 does not induce any detectable proliferation of peroxisomes. In this model, PEX16 would function normally in importing PMPs into preexisting peroxisomes, and would itself be imported into preexisting peroxisomes. In the absence of PEX16, PMP import would cease, peroxisomes could not divide, and the organelle would eventually be lost from the cell population. In addition to this common route of peroxisome formation we propose that PEX16 may, at low efficiency, be targeted to an unknown preperoxisomal structure. The incorporation of PEX16 into such vesicles may convert them to nascent peroxisomes that are able to import other PMPs, and eventually to mature peroxisomes. This model would not only explain the ability of PEX16 to rescue PBD061 cells but would also explain: the presence of a few, large peroxisomes in mutants lacking the PEX11 gene (Erdmann and Blobel, 1995; Marshall et al., 1995); the peroxisome proliferation promoting activity of PEX11 proteins; and the lack of peroxisome proliferation promoting activity for PEX16.

Bottom Line: We also identified human PEX16, a novel integral peroxisomal membrane protein, and found that PBD061 had inactivating mutations in the PEX16 gene.These results demonstrate that peroxisomes do not necessarily arise from division of preexisting peroxisomes.We propose that peroxisomes may form by either of two pathways: one that involves PEX11-mediated division of preexisting peroxisomes, and another that involves PEX16-mediated formation of peroxisomes in the absence of preexisting peroxisomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

ABSTRACT
Zellweger syndrome and related diseases are caused by defective import of peroxisomal matrix proteins. In all previously reported Zellweger syndrome cell lines the defect could be assigned to the matrix protein import pathway since peroxisome membranes were present, and import of integral peroxisomal membrane proteins was normal. However, we report here a Zellweger syndrome patient (PBD061) with an unusual cellular phenotype, an inability to import peroxisomal membrane proteins. We also identified human PEX16, a novel integral peroxisomal membrane protein, and found that PBD061 had inactivating mutations in the PEX16 gene. Previous studies have suggested that peroxisomes arise from preexisting peroxisomes but we find that expression of PEX16 restores the formation of new peroxisomes in PBD061 cells. Peroxisome synthesis and peroxisomal membrane protein import could be detected within 2-3 h of PEX16 injection and was followed by matrix protein import. These results demonstrate that peroxisomes do not necessarily arise from division of preexisting peroxisomes. We propose that peroxisomes may form by either of two pathways: one that involves PEX11-mediated division of preexisting peroxisomes, and another that involves PEX16-mediated formation of peroxisomes in the absence of preexisting peroxisomes.

Show MeSH
Related in: MedlinePlus