Sorting out peroxisome biogenesis

Agrawal et al. describe how different peroxisomal membrane proteins (PMPs) are sorted into distinct vesicles that bud from the ER during de novo peroxisome biogenesis.

Peroxisomes can be generated by the growth and division of preexisting organelles or by a de novo pathway in which preperoxisomal vesicles (ppVs) bud from the ER before fusing to form mature peroxisomes. In the growth and division pathway, newly synthesized PMPs are delivered to peroxisomes by the chaperone Pex19 and its peroxisomal membrane receptor Pex3. Pex19 is also required for ppV budding during de novo biogenesis, but whether Pex3 is involved in this process remained unclear.

Agrawal et al. analyzed how two types of PMP are packaged into ppVs in the yeast P. pastoris. Pex3 and Pex19 were both required to sort the RING-domain PMPs Pex2 and Pex12 (and likely Pex10) to a specialized ER domain called the preperoxisomal ER (pER), where ppVs are formed. Pex3 contains a sorting signal that targets it to this domain. Pex19 linked the RING-domain PMPs to Pex3, allowing them to be co-sorted to the pER and subsequently packaged into two distinct ppVs. In contrast, the docking complex PMPs Pex13, Pex14, and Pex17 were sorted to the pER independently of Pex3 and Pex19, though Pex19 was still required for their incorporation into ppVs.

In mature peroxisomes, the RING-domain and docking complex PMPs form the importomer, which transports peroxisomal matrix proteins into the organelle’s lumen. However, the two types of PMP seemed to occupy slightly distinct regions of the pER, and they weren’t all packaged into the same ppVs, thereby preventing the importomer from assembling prematurely. The researchers now want to investigate the protein and lipid composition of ppVs in more detail.