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Proteins are subject to continuous quality control for optimal proteostasis. The knowledge of peroxisome quality control systems is still in its infancy. Here we show that peroxisomes contain a member of the Lon family of proteases (Pln). We show that Pln is a heptameric protein and acts as an ATP-fueled protease and chaperone. Hence, Pln is the first chaperone identified in fungal peroxisomes. In cells of a PLN deletion strain peroxisomes contain protein aggregates, a major component of which is catalase-peroxidase. We show that this enzyme is sensitive to oxidative damage. The oxidatively damaged, but not the native protein, is a substrate of the Pln protease. Cells of the pln strain contain enhanced levels of catalase-peroxidase protein but reduced catalase-peroxidase enzyme activities. Together with the observation that Pln has chaperone activity in vitro, our data suggest that catalase-peroxidase aggregates accumulate in peroxisomes of pln cells due to the combined absence of Pln protease and chaperone activities.

We have investigated the significance of autophagy in the production of the β-lactam antibiotic penicillin (PEN) by the filamentous fungus Penicillium chrysogenum . In this fungus PEN production is compartmentalized in the cytosol and in peroxisomes. We demonstrate that under PEN-producing conditions significant amounts of cytosolic and peroxisomal proteins are degraded via autophagy. Morphological analysis, based on electron and fluorescence microscopy, revealed that this phenomenon might contribute to progressive deterioration of late subapical cells. We show that deletion of the P. chrysogenum ortholog of Saccharomyces cerevisiae serine-threonine kinase atg1 results in impairment of autophagy. In P. chrysogenum atg1 cells, a distinct delay in cell degeneration is observed relative to wild-type cells. This phenomenon is associated with an increase in the enzyme levels of the PEN biosynthetic pathway and enhanced production levels of this antibacterial compound.

Vitamin D has an important role in skeletal muscles. Previously recognized for its effects on bone, it is now known that vitamin D has a much wider spectrum of usefulness for muscle. Studies indicate that vitamin D deficiency is pandemic. Those affected include the young and otherwise healthy members of the population, including athletes. Controversy exists regarding the amount of supplementation required to reverse deficiency and the relative effect of such a reversal on overall health. This article reviews current data on the role of vitamin D on muscle function, and explores the potential implications of its deficiency and supplementation on physical fitness and athletic performance.

We have analyzed the role of the three members of the Pex11 protein family in peroxisome formation in the filamentous fungus Penicillium chrysogenum. Two of these, Pex11 and Pex11C, are components of the peroxisomal membrane, while Pex11B is present at the endoplasmic reticulum. We show that Pex11 is a major factor involved in peroxisome proliferation. We also demonstrate that P. chrysogenum cells deleted for known peroxisome fission factors (all Pex11 family proteins and Vps1) still contain peroxisomes. Interestingly, we find that, unlike in mammals, Pex16 is not essential for peroxisome biogenesis in P. chrysogenum, as partially functional peroxisomes are present in a pex16 deletion strain. We also show that Pex16 is not involved in de novo biogenesis of peroxisomes, as peroxisomes were still present in quadruple Delta pex11 Delta pex11B Delta pex11C Delta pex16 mutant cells. By contrast, pex3 deletion in P. chrysogenum led to cells devoid of peroxisomes, suggesting that Pex3 may function independently of Pex16. Finally, we demonstrate that the presence of intact peroxisomes is important for the efficiency of beta-lactam antibiotics production by P. chrysogenum. Remarkably, distinct from earlier results with low penicillin producing laboratory strains, upregulation of peroxisome numbers in a high producing P. chrysogenum strain had no significant effect on penicillin production.

Autophagy (macroautophagy) is a bulk degradative pathway by which cytoplasmic components are delivered to the vacuole for recycling. This process is conserved from yeast to human, where it is implicated in cancer and neurodegenerative diseases. During the last decade, many ATG genes involved in autophagy have been identified, initially in Saccharomyces cerevisiae. This review summarizes the knowledge on the molecular mechanisms of autophagy using yeast as model system. Although many of the core components involved in autophagy are conserved from yeast to human, there are, nevertheless, significant differences between these organisms, for example, during autophagy initiation. Autophagy also plays an essential role in filamentous fungi especially during differentiation. Remarkably, in these species autophagy may reflect features of both yeast and mammals. This is exemplified by the finding that filamentous fungi lack the S. cerevisiae clade-specific Atg31 protein, but contain Atg101, which is absent in this clade. A reappraisal of genome data further suggests that, similar to yeast and mammals, filamentous fungi probably also contain two distinct phosphatidylinositol 3-kinase complexes. This review also summarizes the state of knowledge on the role of autophagy in filamentous fungi during differentiation, such as pathogenic development, programmed cell death during heteroincompatibility, and spore formation. Antioxid. Redox Signal. 14, 2271-2287.

Peroxisomes are ubiquitous organelles characterized by a protein-rich matrix surrounded by a single membrane. In filamentous fungi, peroxisomes are crucial for the primary metabolism of several unusual carbon sources used for growth (e. g. fatty acids), but increasing evidence is presented that emphasize the crucial role of these organelles in the formation of a variety of secondary metabolites. In filamentous fungi, peroxisomes also play a role in development and differentiation whereas specialized peroxisomes, the Woronin bodies, play a structural role in plugging septal pores. The biogenesis of peroxisomes in filamentous fungi involves the function of conserved PEX genes, as well as genes that are unique for these organisms. Peroxisomes are also subject to autophagic degradation, a process that involves ATG genes. The interplay between organelle biogenesis and degradation may serve a quality control function, thereby allowing a continuous rejuvenation of the organelle population in the cells.