As a rule, organelles in eukaryotic cells can derive only from pre-existing organelles. Peroxisomes are unique because they acquire their lipids and membrane proteins from the endoplasmic reticulum (ER), whereas they import their matrix proteins directly from the cytosol. We have discovered that peroxisomes are formed via heterotypic fusion of at least two biochemically distinct preperoxisomal vesicle pools that arise from the ER. These vesicles each carry half a peroxisomal translocon complex. Their fusion initiates assembly of the full peroxisomal translocon and subsequent uptake of enzymes from the cytosol. Our findings demonstrate a remarkable mechanism to maintain biochemical identity of organelles by transporting crucial components via different routes to their final destination.

We demonstrate that the entry of peroxisomal membrane proteins (PMPs) into the ER is mediated by the general ER import machinery. Within the ER, PMPs attain their correct topology and subsequently travel to peroxisomes. Our results show that the ER forms an obligate requirement to maintain peroxisomes in multiplying cells.

Looks can be deceiving. Although peroxisomes appear to be simple organelles, their formation and maintenance pose unique challenges for the cell. The birth of new peroxisomes starts at the endoplasmic reticulum (ER), which delivers lipids and membrane proteins. To form a new peroxisomal compartment, ER-derived preperoxisomal vesicles carrying different membrane proteins fuse, allowing the assembly of the peroxisomal translocon. To complete formation, peroxisomes import their soluble proteins directly from the cytosol using the newly assembled translocon. Together with the ER-derived biogenic route, peroxisomal fission and segregation subsequently maintain the cellular peroxisome population. In this review we highlight the latest insights on the life cycle of peroxisomes and show how the new cell biology concept of peroxisome formation affects our thinking about peroxisome-related diseases and their evolutionary past. The future challenge lies in the identification of all the proteins involved in this elaborate biogenic process and the dissection of their mechanism of action.

No abstract

Eukaryotic cells contain functionally distinct, membrane enclosed compartments called organelles. Here we like to address two questions concerning this architectural lay out. How did this membrane complexity arise during evolution and how is this collection of organelles maintained in multiplying cells to ensure that new cells retain a complete set of them. We will try to address these questions with peroxisomes as a focal point of interest.