Benzbromarone, a uricosuric drug, reportedly causes hepatic hypertrophy accompanied by proliferation of peroxisomes in rats. To elucidate the mechanisms underlying induction of peroxisome proliferation by benzbromarone, we examined binding affinity for peroxisome proliferator-activated receptor alpha (PPARalpha) and gamma (PPARgamma), and effects on the binding activity of PPARs with peroxisome...

We have combined classical subcellular fractionation with large-scale quantitative mass spectrometry to identify proteins that enrich specifically with peroxisomes of Saccharomyces cerevisiae. In two complementary experiments, isotope-coded affinity tags and tandem mass spectrometry were used to quantify the relative enrichment of proteins during the purification of peroxisomes. Mathematical mo...

This chapter concerns one branch of the peroxisome import pathway for newly-synthesized peroxisomal proteins, specifically the branch for matrix proteins that contain a peroxisome targeting sequence type 2 (PTS2). The structure and utilization of the PTS2 are discussed, as well as the properties of the receptor, Pex7p, which recognizes the PTS2 sequence and conveys these proteins to the common ...

Evidence is accumulating that damaged components of eukaryotic cells are removed by autophagic degradation (e.g., mitophagy). Here we show that peroxisomes that are damaged by the abrupt removal of the membrane protein Pex3 are massively and rapidly degraded even when the cells are placed at peroxisome-inducing conditions and hence need the organelles for growth. Pex3 degradation was induced by...

In the fungus Penicillium chrysogenum, penicillin (PEN) production is compartmentalized in the cytosol and in peroxisomes. Here we show that intact peroxisomes that contain the two final enzymes of PEN biosynthesis, acyl coenzyme A (CoA):6-amino penicillanic acid acyltransferase (AT) as well as the side-chain precursor activation enzyme phenylacetyl CoA ligase (PCL), are crucial for efficient P...

Feeding rats with a diet containing 0.25% clofibrate for 2 weeks elevated the hepatic NAD+ and total nicotinate levels significantly. Other peroxisome proliferators, such as 2-(4-chlorophenoxy)propionic acid and di(2-ethylhexyl)phthalate, had similar effects. When rats were fed the control diet without clofibrate for 1 week after 2 weeks of the clofibrate diet, the hepatic NAD+ level returned t...

The biogenesis of peroxisomal matrix and membrane proteins is substantially different from the biogenesis of proteins of other subcellular compartments, such as mitochondria and chloroplasts, that are of endosymbiotic origin. Proteins are targeted to the peroxisome matrix through interactions between specific targeting sequences and receptor proteins, followed by protein translocation across th...

In the yeast Hansenula polymorpha peroxisomes are selectively degraded upon a shift of cells from methanol to glucose-containing media. We identified the H. polymorpha TUP1 gene by functional complementation of the peroxisome degradation deficient mutant pdd2-4. Tup1 proteins function in transcriptional repression of specific sets of genes involved in various cellular processes. Our combined da...

Several decades ago, fibrates were approved for the treatment of dyslipidemia, whereas thiazolidinediones were screened in animal models to improve glucose homeostasis and were subsequently developed for the treatment of type 2 diabetes mellitus. Relatively recently, these drugs were found to act via peroxisome proliferator-activated receptors, nuclear receptors that control lipid metabolism an...