Peroxisome Dynamics: Molecular Players, Mechanisms, and (Dys)functions

Figure 1

Model of peroxisome dynamics. New peroxisomes can be formed de novo from the ER or by asymmetric growth and division of preexisting organelles. In the de novo pathway, a select set of PMPs is inserted into the ER via the Sec61p translocon (or the GET complex) and sequestered into specialized Pex3p-containing ER exit sites from which smoothed vesicles are pinched off in a Pex19p-dependent manner. These peroxisomal precompartments subsequently develop into mature peroxisomes that are capable of importing matrix proteins. The latter process can be divided into several different stages: cargo-recognition by a PTS receptor; docking of the PTS receptor-cargo complexes at the peroxisomal membrane (the Pex7p-cargo complexes require auxiliary factors for import); cargo translocation across the peroxisomal membrane and cargo release into the peroxisomal matrix; receptor recycling. The latter event requires the involvement of the receptor export module, which ubiquitinates the receptor and extracts it from the peroxisomal membrane. Peroxisomes can also grow in number and size by a complex asymmetric multistep maturation pathway, a process that involves peroxisome elongation, membrane constriction, and organelle fission. Members of the Pex11p-family of peroxins are involved in the elongation process, the components of the constriction machinery are not yet known, and the fission machinery comprises soluble dynamin-like proteins that are recruited to the peroxisomal membrane by Fis1p and/or Mff (with or without the help of adaptor proteins). Importantly, as “old” matrix proteins are retained within the mother organelle, this leads to matrix protein asymmetry. During their life cycle, peroxisomes are also subject to rigorous quality control: oxidatively damaged matrix proteins are degraded by a peroxisomal Lon protease, superfluous PMPs are extracted from the peroxisomal membrane and degraded by the proteasome, and dysfunctional organelles are removed by pexophagy. The triggers and mechanisms underlying the quality control of peroxisomes have only recently begun to be elucidated. Note that (i) peroxins are indicated in white numbers in red (evolutionarily conserved peroxins) or orange (species-specific peroxins) circles; (ii) grey circles represent factors that are also involved in nonperoxisomal processes; (iii) more details can be found in the text.