The long-term objectives of this project are to understand the manner and the mechanisms by which the peroxisome is formed in rat liver, and the means by which this process is regulated.
The specific aims of the present application are: 1) To elucidate the properties and the biogenesis of the major integral membrane protein (previous work has focused on the core and matrix proteins). 2) To investigate the apparent organization of some matrix proteins into supramolecular assemblies. 3) To investigate the details of post-translational uptake of proteins into peroxisomes both in vitro and in vivo, considering possible interactions with the membrane. The experiments proposed will decide unequivocally between several hypothetical models of peroxisome biogenesis. 4) To check an integral membrane protein that might be common to mitochondria, peroxisomes and endoplasmic reticulum. 5) To investigate the molecular mechanism(s) by which the hypolipidemic drug, clofibrate, induces a major peroxisomal bifunctional protein. Methods to be employed in this research include analytical and preparative cell fractionation, enzyme assays, electron microscopy and EM autoradiography, SDS-PAGE, cell-free translations, immunoaffinity chromatography and peptide mapping. These methods are in routine use in the laboratory. Our understanding of peroxisomal metabolism has increased considerably in recent years, and was the subject of an International Symposium at the New York Academy of Sciences in September, 1981. Peroxisomal functions include thermogenic respiration, lipid metabolism, gluconeogenesis, alcohol metabolism and purine catabolism. Peroxisomes are altered in several diseases, including atherosclerosis, Zellweger's syndrome, Reye's disease and cancer. An understanding of peroxisomal function and regulation at the molecular level may eventually be of practical value in understanding and treating these conditions.
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