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Peroxisome formation from pre-peroxisomal vesicles and remnants

The peroxisome is an organelle present in all eukaryotes and it provides highly diverse and often species-specific functions in cellular metabolism. EU researchers made major headway into the formation pathways in play for this organelle.
Peroxisome formation from pre-peroxisomal vesicles and remnants
Despite their indisputable importance, there is incomplete knowledge regarding the formation of peroxisomes, some theories still being hotly debated. The PEROXISCOPY (Morphogenesis of de novo peroxisome formation) project has cleared some of the mystery around how peroxisomes are formed and the biochemistry involved.

The main focus of the research was the peroxisomal biogenesis factors (peroxins; PEX) group involved in de novo peroxisome biogenesis. Formation of peroxisomes involves the Pex3 protein and the researchers used yeast mutants devoid of the PEX3 gene to show for the first time the presence of pre-peroxisomal vesicles in this mutant. The results show that peroxisomes are not formed from scratch from the endoplasmic reticulum membrane system when the PEX3 gene is reintroduced. Instead, Pex3 protein sorts to the immature pre-peroxisomal structures in these mutant cells and then prompts maturation of the organelles.

The scientists also looked at two key enzymes, Pex1 and Pex6. They showed that these proteins play an important part in the import of matrix proteins, but not in fusion of pre-peroxisomal vesicles as proposed earlier by other research results. Upon reintroduction of Pex1, matrix protein import was restored and the peroxisomal ghosts rapidly developed into peroxisomes.

As there is evidence that maintenance of peroxisome number is crucial for cell physiology, the researchers also investigated the proliferation of the peroxisomes by fission. Pex11 remodels the peroxisomal membrane during fission and results showed that this protein exhibits GTPase activity and thereby activates an enzyme (Dnm1) necessary for subsequent fission.

Collaboration with a laboratory with an excellent track record in peroxisome research prompted a rerun of investigations regarding the role of Pex19 in pre-peroxisomal vesicle formation. Work on this is anticipated to continue using cryo-electron microscopy to visualise the formation of peroxisomes as well as the mature organelles.

The work has been published in high-profile journals including the Journal of Cell Biology (2x) and PNAS. PEROXISCOPY research has confirmed that despite their unassuming appearance, peroxisomes play a key role in the maintenance of cell physiology and moreover that the former models regarding their formation require adaptation.

Related information


Pex, peroxisome, organelle, yeast, microscopy
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