title: A peroxisomal lon protease and peroxisome degradation by autophagy play key roles in vitality of Hansenula polymorpha cells.
abstract: In eukaryote cells various mechanisms exist that are responsible for the removal of non-functional proteins. Here we show that in the yeast Hansenula polymorpha (H. polymorpha) a peroxisomal Lon protease, Pln, plays a role in degradation of unfolded and non-assembled peroxisomal matrix proteins. In addition, we demonstrate that whole peroxisomes are constitutively degraded by autophagy during normal vegetative growth of WT cells. Deletion of both H. polymorpha PLN and ATG1, required for autophagy, resulted in a significant increase in peroxisome numbers, paralleled by a decrease in cell viability relative to WT cells. Also, in these cells and in cells of PLN and ATG1 single deletion strains, the intracellular levels of reactive oxygen species had increased relative to WT controls. The enhanced generation of reactive oxygen species may be related to an uneven distribution of peroxisomal catalase activities in the mutant cells, as demonstrated by cytochemistry. We speculate that in the absence of HpPln or autophagy unfolded and non-assembled peroxisomal matrix proteins accumulate, which can form aggregates and lead to an imbalance in hydrogen peroxide production and degradation in some of the organelles.
authors.affiliation: Eukaryotic Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, Haren, The Netherlands.
authors.forename: Eda Bener
authors.initials: EB
authors.lastname: Aksam
authors.forename: Anne
authors.initials: A
authors.lastname: Koek
authors.forename: Jan A K W
authors.initials: JA
authors.lastname: Kiel
authors.forename: Stefanie
authors.initials: S
authors.lastname: Jourdan
authors.forename: Marten
authors.initials: M
authors.lastname: Veenhuis
authors.forename: Ida J
authors.initials: IJ
authors.lastname: van der Klei
mesh_terms: D001343:Autophagy / Q000502:physiology*; D002374:Catalase / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D020675:Peroxisomes / Q000201:enzymology* / Q000648:ultrastructure; D010802:Phylogeny; D010843:Pichia / Q000166:cytology* / Q000201:enzymology* / Q000254:growth & development / Q000648:ultrastructure; D049070:Protease La / Q000737:chemistry / Q000378:metabolism*; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012995:Solubility
chemical_list: D005656:Fungal Proteins; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D002374:Catalase; D049070:Protease La