Function of peroxisome in mammal and analysis of the fatty acid oxidation system by photoaffinity labeling

Peroxisomes play an essential role in a number of important metabolic pathways including oxidation of fatty acids, and synthesis of ether phospholipids and bile acids. Long, very long, and branched-chain fatty acid-CoA as well as intermediate metabolites for bile acid synthesis are transported into peroxisomes through ATP-binding cassette (ABC) transporters, ABCD1-3 on the membranes and oxidized by α- and ß-oxidation enzymes. Mutation of these transporters and enzymes causes severe peroxisomal disorders. Characterization of molecular mechanism of the substrate transport and the enzyme reaction is an important issue to figure out the role of these proteins in lipid metabolism under physiological and pathological conditions. Recently precise structure of several enzymes involved in peroxisomal fatty acid oxidation has been revealed by the studies based on X-ray crystallography and NMR spectroscopy. However, the molecular mechanisms of these proteins, especially in terms of substrate binding, have not yet been elucidated in detail. Photoaffinity labeling has been a powerful tool to find specific region for the binding of the substrate using a ligand with a photoactivatable group. Here, we first review biogenesis and function of peroxisome, and then focus our attention to molecular recognition of substrate by peroxisomal proteins including ABC transporters by photoaffinity labeling.