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. 2010 Oct;51(10):2863–2895. doi: 10.1194/jlr.R005959

Fig. 1.

Fig. 1.

Peroxisome biogenesis in humans. A: A simplified scheme for protein import in mammalian peroxisomes under normal conditions and involved peroxins, indicated by their PEX number and arranged according to known interactions, is shown. The complex of PTS1-matrix proteins (in green) and one of the PEX5 isoforms, formed in the cytoplasm, will dock at the membrane, followed by translocation involving the RING peroxins PEX2, 10, and 12 (dashed arrows). After cargo release, PEX5 is recycled to the cytoplasm with the help of PEX1, 6, and 26 (dashed arrow). The role of mono- and polyubiquitination of PEX5 in this process is not displayed. Import of PTS2-matrix proteins (in orange), captured by PEX7, is mediated by the long PEX5 isoform. After import, some PTS1 proteins are proteolytically processed (T), and the targeting signal of PTS2-proteins is removed (ACAA1, thiolase; PHYH, AGPS). Newly synthesized PMPs (in blue) can interact with PEX19 in the cytoplasm (or with the membrane associated PEX19), followed by docking and membrane insertion. Peroxins playing a role in PMP targeting are depicted in different shades of blue. In the absence of a functional PEX7, PTS2 proteins are not imported and processed and are degraded in the cytoplasm (faintly colored), but the matrix is still filled with PTS1 proteins (B). This condition results in RCDP type I. Patients with RCDP type I have rhizomelia and congenital cataracts (notice the spectacles in this 19-month-old infant). When peroxins involved in PTS1 import are missing, e.g., PEX14 (C), peroxisomes are empty (ghosts) causing the severe ZS. Both PTS1 and PTS2 proteins remain cytoplasmic and unprocessed and can be degraded. The picture shows a very hypotonic baby with head malformation, low ear implantation, and hepatomegaly. In cases where PEX19 or other peroxins involved in PMP import are mutated (not shown), all peroxisomal proteins remain in the cytoplasm or are degraded, and no ghosts can be observed. Pictures courtesy of Dr. L. Van Maldergem, Centre de Génétique Humaine, Université de Liège, Belgium (B) and Dr. J. Jaeken, UZ-Leuven, Belgium (C) with informed consent of the parents.