Peroxisomal Protein Import The Paradigm Shifts

oxisomal matrix proteins are imported into the organelle from their site of synthesis on free cytoplasmic ribo-somes. This observation led to the classical model of peroxisome proliferation in which existing peroxisomes Amherst, Massachusetts 01003 increase in size via the direct import of proteins from the cytoplasm, and divide by fission or budding (La-zarow and Fujiki, 1985). As such, the biogenesis of per-Organelle biogenesis in eukaryotes is dependent on a oxisomes was classified with those of mitochondria and set of highly specific intracellular trafficking systems chloroplasts, and it appeared that peroxisomal protein that mediate the targeting of newly synthesized or na-import would represent a variation on the theme ob-scent polypeptides to their appropriate cellular com-served in these other organelles. In chloroplasts and partments. Recent developments from the study of pro-mitochondria, signal receptor systems function to direct tein import into peroxisomes challenge the classical polypeptides to the translocation machinery (translo-paradigm in which proteins are targeted to the surface of con) at the organelle surface. The polypeptide is subse-organelles and subsequently threaded through protein-quently threaded vectorially through a gated protein-conducting channels of defined dimension. A report by conducting channel component of the translocon with Dammai and Subramani (2001) in the April 20 issue of the aid of molecular chaperones in an unfolded confor-Cell demonstrates that the major receptor for targeting mation (Figure 1A) (Schatz and Dobberstein, 1996). As proteins to the peroxisomal matrix, Pex5p, shuttles be-such, a single translocon of defined dimensions can tween the cytoplasm and matrix during the import cycle. accommodate a vast array of polypeptides of diverse The study follows earlier work demonstrating that the size and primary sequence while maintaining the critical membrane translocation apparatus for peroxisomal ma-membrane permeability barrier. trix proteins can expand to accommodate fully folded The classification of peroxisomal protein import with and oligomeric substrates. Surprisingly, the proposed that of import into chloroplasts and mitochondria was mechanism of peroxisomal import in which soluble re-soon challenged when evidence accumulated that per-ceptors shuttle folded and assembled complexes into oxisomes could import fully folded and oligomeric pro-the organelle more closely resembles that of nucleocy-teins (Figure 1B). Although at first controversial, the toplasmic transport than that of protein import into or-ability of the peroxisomal translocation machinery to ganelles such as the ER, mitochondria, and chloro-accommodate large folded substrates was definitively plasts. These developments highlight the remarkable established by the demonstration that 9 nm colloidal flexibility of membrane translocation machines to …