Background: A putative Lon protease has been identified in peroxisomes of various species (Pln). Results: Pln is an ATP-dependent protease that digests unfolded substrates e.g. oxidatively damaged catalase-peroxidase, and displays chaperone-like activity, circumventing accumulation of protein aggregates in peroxisomes that compromise organelle function. Conclusion: Pln is a bifunctional protein with chaperone and protease activities. Significance: Pln is crucial for peroxisome proteostasis.

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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.

We have investigated the significance of autophagy in the production of the ␤-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.The discovery of penicillins in 1929 by Fleming is probably the most important observation in the history of therapeutic medicine development. Penicillins belong to the group of ␤-lactam antibiotics and are produced as secondary metabolites by several filamentous fungi (3). For industrial production the filamentous fungus Penicillium chrysogenum is used. The first steps of the penicillin (PEN) biosynthetic pathway take place in the cytosol. The amino acid precursors L-␣-aminoadipic acid (L-␣-AAA), L-cysteine, and L-valine are condensed into the tripeptide ␦-(L-␣-aminoadipyl)-L-cysteinyl-D-valine (ACV) by the enzyme ACV synthetase (ACVS). Isopenicillin N synthase (IPNS) catalyzes the oxidative ring closure of the linear ACV tripeptide, which leads to the formation of isopenicillin N (IPN), which has a bicyclic ring structure. The final step of penicillin biosynthesis, in which the hydrophilic L-␣-AAA side chain of IPN is exchanged for a hydrophobic acyl group, occurs inside peroxisomes via isopenicillin N acyltransferase (IAT) and phenylacetyl coenzyme A ligase (PCL) (2).Peroxisomes are single-membrane-bound organelles present in all eukaryotes. These cellular compartments are involved in various metabolic pathways. The importance of peroxisomes for efficient penicillin production in P. chrysogenum has been well documented (23,24). Muller et al. (24) first suggested a correlation between penicillin production and the volume fraction of peroxisomes. Later, it was shown that the high-producing strain DS17690 has enhanced numbers of these organelles relative to the original NRRL 1951 strain (41). Moreover, induction of peroxisome proliferation via overproduction of Pex11 in P. chrysogenum resulted in enhanced levels of penicillin production in two laboratory strains (14).A remarkable feature of filamentous fungi is the differentiation of cells along the hyphae. These structures can be divided into actively growing regions (apical cells), metabolically active nongrowing regions (subapical cells), and the oldest part of the hyphae, which are comprised of degen...

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.