Fig. 9.

Peroxisomal biogenesis through interorganellar contact sites and transport pathways. Peroxisomal contact sites (left box, top panel) shows a confocal image of peroxisomes (yellow, anti-PMP70) in contact with ER (magenta, anti-KDEL) and mitochondria (blue, anti-TOM20) within a COS7 cell. These mammalian contacts were shown to require ACBD5 and VapB, as described in the text. Bottom panel shows an electron micrograph of a mouse liver cell illustrating direct contacts between a peroxisome (yellow), the ER (magenta) and a mitochondria (blue). A lipid droplet is also seen in direct contact with the mitochondria (on top). Many metabolites are modified by enzymes within multiple compartments, particularly bile acids within the liver that use the ‘catalytic triad’ of organelles seen here between the ER/mitochondria and peroxisomes. The emerging model of de novo peroxisomal biogenesis in mammalian cells is shown in the right panel. Pex16 is targeted to the ER, whereas Pex3 and Pex14 target the mitochondria in Zellweger patient fibroblasts lacking peroxisomes. Each is sorted into vesicular profiles that merge to form an import-competent peroxisome that continues to grow and divide. The molecular mechanisms and regulation of peroxisomal contact site formation and biogenesis are only just beginning to be understood