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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK019394-11
Application #
3226355
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1976-05-01
Project End
1988-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
11
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Rockefeller University
Department
Type
Graduate Schools
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Nair, Devi M; Purdue, P Edward; Lazarow, Paul B (2004) Pex7p translocates in and out of peroxisomes in Saccharomyces cerevisiae. J Cell Biol 167:599-604
Lazarow, Paul B (2003) Peroxisome biogenesis: advances and conundrums. Curr Opin Cell Biol 15:489-97
Yang, X; Purdue, P E; Lazarow, P B (2001) Eci1p uses a PTS1 to enter peroxisomes: either its own or that of a partner, Dci1p. Eur J Cell Biol 80:126-38
Purdue, P E; Lazarow, P B (2001) Peroxisome biogenesis. Annu Rev Cell Dev Biol 17:701-52
Purdue, P E; Lazarow, P B (2001) Pex18p is constitutively degraded during peroxisome biogenesis. J Biol Chem 276:47684-9
Santos, M J; Henderson, S C; Moser, A B et al. (2000) Peroxisomal ghosts are intracellular structures distinct from lysosomal compartments in Zellweger syndrome: a confocal laser scanning microscopy study. Biol Cell 92:85-94
Purdue, P E; Skoneczny, M; Yang, X et al. (1999) Rhizomelic chondrodysplasia punctata, a peroxisomal biogenesis disorder caused by defects in Pex7p, a peroxisomal protein import receptor: a minireview. Neurochem Res 24:581-6
Purdue, P E; Yang, X; Lazarow, P B (1998) Pex18p and Pex21p, a novel pair of related peroxins essential for peroxisomal targeting by the PTS2 pathway. J Cell Biol 143:1859-69
Purdue, P E; Zhang, J W; Skoneczny, M et al. (1997) Rhizomelic chondrodysplasia punctata is caused by deficiency of human PEX7, a homologue of the yeast PTS2 receptor. Nat Genet 15:381-4
Zhang, J W; Lazarow, P B (1996) Peb1p (Pas7p) is an intraperoxisomal receptor for the NH2-terminal, type 2, peroxisomal targeting sequence of thiolase: Peb1p itself is targeted to peroxisomes by an NH2-terminal peptide. J Cell Biol 132:325-34

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