PEX19dependent

PEX19dependent refers to a subset of peroxisomal membrane proteins (PMPs) whose targeting and insertion into the peroxisomal membrane require the cytosolic chaperone/receptor PEX19. In many organisms, PMPs can be categorized as PEX19-dependent or PEX19-independent, with the former relying on PEX19 for stabilization in the cytosol and for delivery to the peroxisome.

Mechanistically, PEX19 acts as a soluble receptor and chaperone that recognizes PMPs through specific binding motifs. It binds newly synthesized PMPs in the cytosol, preventing aggregation, and escorts them to the peroxisomal membrane. At the membrane, PEX19 interacts with docking factors such as PEX3, enabling the insertion or stabilization of PMPs into the lipid bilayer. This pathway helps assemble the peroxisomal membrane and import machinery.

The concept of PEX19dependency is used to understand differences in PMP biogenesis across species and under different cellular conditions. While many PMPs are PEX19-dependent, some PMPs can reach and integrate into the peroxisomal membrane via alternative, PEX19-independent routes. The relative reliance on PEX19 can influence peroxisome biogenesis efficiency and the response to genetic perturbations.

Clinical relevance arises because mutations in PEX19 disrupt PMP targeting, compromising peroxisome formation and function. Such defects contribute to peroxisome biogenesis disorders, underscoring the essential role of the PEX19-dependent pathway in maintaining peroxisomal membranes and their associated metabolic activities.

See also: peroxisome, peroxins, PEX3, PEX19, peroxisomal membrane proteins, peroxisomal biogenesis disorders.