Peroxisome structure, function, and biogenesis--human patients and yeast mutants show strikingly similar defects in peroxisome biogenesis.

Peroxisomes are found in almost all eukaryotic cells. Two major functions of the organelle are in lipid metabolism: peroxisomes catalyze the initial steps in the biosynthesis of plasmalogens, which are phospholipids that are present in large amounts in myelin. Peroxisomes also catalyze the beta-oxidation of fatty acids; this pathway is essential for the catabolism of a variety of substrates that are not oxidized by mitochondria. A third important function is in cellular respiration, involving the metabolism of H2O2, for which the peroxisome is named. Peroxisomes increase in size by the post-translational import of newly synthesized proteins from the cytosol; these pre-existing peroxisomes divide to form new peroxisomes. Proteins are targeted to peroxisomes by three different types of topogenic sequences, and it is hypothesized that a receptor exists for each type. The newly made proteins are translocated through the peroxisomal membrane into the interior by a machinery that is energized by ATP hydrolysis. Human patients and yeast mutants have remarkably similar defects in peroxisome biogenesis. Some such mutants are defective in the import of a subset of peroxisomal proteins that share a topogenic sequence type; other mutants fail to import all newly made proteins into peroxisomes, regardless of the type of targeting sequence they possess. These mutants might be defective in receptors and in translocation machinery components, respectively. Cloned genes that are essential for peroxisome biogenesis encode diverse proteins: some likely receptors, some transmembrane proteins possibly involved in translocation, and others hydrophilic proteins that may play other roles in peroxisome assembly.