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Eukaryotic cells contain intracellular membrane-surrounded compartments (organelles) providing diverse optimal environments for specific metabolic pathways. Among these organelles peroxisomes participate in many metabolic processes, most notably the degradation of fatty acids and the glyoxylate cycle. Synthesis of peroxisomes from already existing ones or through a de novo biogenesis pathway is tightly regulated in agreement with the metabolic status of the cell and balanced using a specific degradation process called pexophagy. A network of interacting proteins guarantees the biogenesis of functional peroxisomes, the translocation of peroxisomal proteins across and into the peroxisomal membrane, and the control of size, shape and number of these compartments. Our research interests are the detailed mechanism of the de novo biogenesis process, a feature unique for peroxisomes, and the communication of the glyoxylate cycle enzymes across the peroxisomal membrane.
Employing the yeast Saccharomyces cerevisiae as model system we generate various mutants with defects in the inheritance of peroxisomes to the daughter cells and analyse the re-appearance of peroxisomes in cells harboring all possible single deletions of yeast genes (synthetic genetic array). Their growth behavior on various media is analysed, too. Yeast mutants carrying mutations in proteins catalyzing glyoxylate cycle reactions are grown on various carbon sources in the presence or absence of metabolites, and their glyoxylate cycle activities are followed. The corresponding enzymes are located on both sides of the peroxisomal membrane, which does not represent a barrier for intermediates but controls the velocity of the continuous flux.
After a PhD in Chemistry from the University of Vienna in 1979 Andreas Hartig spent postdoctoral years at the NIH, Bethesda, USA, at Rutgers University, Piscataway, USA, and in Vienna at the Department of Biochemistry with the late Prof. Dr. Helmut Ruis, which stimulated his interest in cellular and molecular biology of yeast. Since 1986 a member of the faculty he retired in October 2017.
Most peroxisomal matrix proteins contain a C-terminal targeting signal, which is 12 amino acids long with the ultimate 3 amino acids buried in the binding pocket of Pex5p. Organism-specific differences in recognition are due to different affinities of the receptors to the 12-amino-acid signal. A predictor for the C-terminal targeting signal was established.
The C-terminal peroxisomal targeting signal is recognized by the C-terminal half of Pex5p representing a TPR-repeat. Pex5p in turn is recognized by Pex14p, which is part of the peroxisomal translocation machinery.
Pex11 protein family members are membrane elongation factors that coordinate peroxisome proliferation and maintenance. In yeast, the Pex25-protein turned out to be a major player in the de novo biogenesis process.
Enzymes using acetylCoA and participating in the glyoxylate cycle are located inside peroxisomes, the other participants remain outside the organelles. With a membrane permeable for small solutes up to approx. 300D and impermeable for nucleotides the formation of a transient cross-membrane metabolon appears a likely hypothesis enabling the swift exchange of metabolites.
Permeability of the peroxisomal membrane: lessons from the glyoxylate cycle.
Kunze M and Hartig A
A Subtle Interplay between Three Pex11 Proteins Shapes de novo Formation and Fission of Peroxisomes.
Huber, Anja; Koch, Johannes; Kragler, Friedrich; Brocard, Cécile; Hartig, Andreas
PEX11 family members are membrane elongation factors that coordinate peroxisome proliferation and maintenance.
Koch, Johannes; Pranjic, Kornelija; Huber, Anja; Ellinger, Adolf; Hartig, Andreas; Kragler, Friedrich; Brocard, Cécile