The peroxisome is one of many cellular organelles. Unlike mitochondria and chloroplasts, peroxisomes are delineated by a single membrane and as such are considered to be structurally simple. Compared to mitochondria and chloroplasts, peroxisomes are small, measuring only 0.2-1.7 microns in diameter. Peroxisomes function in several critical biochemical processes. In germinated fat-storing seeds, peroxisomes are involved in lipid mobilization; in leaves of C3 plants they participate in photorespiration; and in nodule-forming plants they play an important role in converting recently fixed nitrogen into organic compounds. One important peroxisomal enzyme is catalase, a matrix enzyme that converts toxic hydrogen peroxide to water.
Until recently, there was no strict consensus about how peroxisomes are formed or maintained in plant cells. In a review article in the June issue of Trends in Plant Science, Robert T. Mullen (University of Guelph, Canada) and C. Robb Flynn and Richard N. Trelease at Arizona State University have addressed this question critically. The authors discuss a hypothesis for peroxisome biogenesis introduced in 1970 in which it was proposed that peroxisomes arise from rough ER (RER) by budding. This model, known as the “ER-vesiculation” model, was abandoned soon after its conception when a number of new findings on the formation and maintenance of peroxisomes provided evidence against a role for the ER. Among these were the observations that peroxisomal proteins are synthesized post-translationally and imported directly into the organelle. These findings indicate that peroxisomal proteins are formed on free polysomes in the cytosol and not on the ER. Based on these data, “the growth and division model” was proposed. In this model, peroxisomes grow in size during the lifespan of the cell and proliferate by fission of mature organelles, not unlike chloroplasts or mitochondria. An important finding in support of the “growth and division model” was the identification of yeast, mammalian, and a few plant peroxin (Pex) genes whose products are involved in peroxisome assembly and peroxisomal membrane formation. Some of these Pex genes code for proteins such as Pex5p, Pex7p, Pex13p, Pex14p and Pex17p. Pex5p and Pex7p serve as soluble receptors in the cytosol, while Pex14p, Pex14p and Pex17p constitute part of a “docking complex” on the peroxisomal boundary membrane.
The authors review current thinking on how matrix-destined proteins are imported into mature peroxisomes in the “growth and division model”. In the cytosol, the receptor proteins Pex5p and Pex7p combine with proteins bearing peroxisomal targeting signals. These targeting signals are known as PTS1 and PTS2, respectively. The receptor and PTS-containing cargo protein complex then moves to the docking complex at the surface of the peroxisomal membrane. After docking, the cargo protein enters the peroxisomal matrix and receptors are either cycled back to the cytosol or are imported into the interior of the peroxisome along with their cargo. The delivered cargo (and associated receptors) crosses the boundary membrane as monomers or oligomers in a folded conformation.
The “growth and division model” presumes that all membrane proteins destined for the peroxisome are sorted directly from their site of synthesis in the cytosol. However, recent studies show that the sorting of some peroxisomal membrane proteins (PMPs) does not follow a pathway directly from the cytosol. Instead, several PMPs are sorted indirectly to peroxisomes via the ER. In light of this body of recent evidence, “the growth and division model” has been modified to recognize the role of ER in peroxisome formation. According to the proposed new model, peroxisome biogenesis includes the direct sorting of some PMPs from the cytosol. Evidence exists for at least three different types of peroxisomal structures: (1) preperoxisomal vesicles that have bud from a specialized region of the ER (termed peroxisomal ER) and that are en route to nascent or mature peroxisomes, (2) nascent peroxisomes that were formed when two or more preperoxisomal vesicles are fused, and (3) “mature” peroxisomes already present within the cell. In some instances, the fusion product of a preperoxisomal vesicle and a pre-existing mature peroxisome may undergo fission and give rise to additional “nascent” peroxisomes. Matrix proteins are synthesized in the cytosol and post-translationally imported into one or more of these types of peroxisomes. However, a subset of PMPs is thought to be targeted to the ER and become incorporated into the peroxisome via an ER-mediated event. Evidence for the existence of ER-derived preperoxisomal vesicles involved in PMP export has been obtained in both plants and yeast. For example, the inhibition of vesiculation by the fungal toxin Brefeldin A (BFA) results in the accumulation of peroxisomal matrix proteins in the cytosol and membrane proteins in the ER in tobacco BY-2 cells. In the yeast Hansenula polymorpha, treatment with BFA results in both matrix and membrane peroxisomal proteins accumulating in the ER.
The modified hypothesis gives a satisfactory explanation of events leading to the formation of peroxisomes in yeast and plant cells but does not account for peroxisome formation in mammalian cells, where available data do not support involvement of the ER. Yeast PMPs that are sorted to the ER before being incorporated into peroxisomes had no requirement for ER sorting when tested in mammalian systems. In addition, peroxisome biogenesis was also not affected in mammalian cells when transport of ER-derived secretory vesicles was blocked.
Despite the lack of involvement of the ER during peroxisome biogenesis in mammals, the authors describe another interesting but enigmatic situation: ten of the recently discovered Arabidopsis peroxin genes show striking amino acid identity with their homologs from mammals – much more than they show similarity with their yeast counterparts. The authors believe that the recent identification of 15 Arabidopsis homologs of yeast and mammalian peroxins genes, most of which encode membrane proteins, will help the researchers gain insight into the mechanisms of PMP sorting. Ultimately, this will yield a better understanding of the biogenesis of peroxisomes.