PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis

Peroxisomes are components of virtually all eukaryotic cells. While much is known about peroxisomal matrix protein import, our understanding of how pe roxisomal membrane proteins (PMPs) are targeted and inserted into the perox isome membrane is extremely limited. Here, we show that PEX19 binds a broad spectrum of PMPs, displays saturable PMP binding, and interacts with regio ns of PMPs required for their targeting to peroxisomes. Furthermore, misloc alization of PEX19 to the nucleus leads to nuclear accumulation of newly sy nthesized PMPs. At steady state, PEX19 is bimodally distributed between the cytoplasm and peroxisome, with most of the protein in the cytoplasm. We pr opose that PEX19 may bind newly synthesized PMPs and facilitate their inser tion into the peroxisome membrane. This hypothesis is supported by the obse rvation that the loss of PEX19 results in degradation of PMPs and/or misloc alization of PMPs to the mitochondrion.