Peroxisome interactions and cross-talk with other subcellular compartments in animal cells.

Peroxisomes are remarkably plastic and dynamic organelles, which fulfil important functions in hydrogen peroxide and lipid metabolism rendering them essential for human health and development. Despite great advances in the identification and characterization of essential components and molecular mechanisms associated with the biogenesis and function of peroxisomes, our understanding of how peroxisomes are incorporated into metabolic pathways and cellular communication networks is just beginning to emerge. Here we address the interaction of peroxisomes with other subcellular compartments including the relationship with the endoplasmic reticulum, the peroxisome-mitochondria connection and the association with lipid droplets. We highlight metabolic cooperations and potential cross-talk and summarize recent findings on peroxisome-peroxisome interactions and the interaction of peroxisomes with microtubules in mammalian cells.

Self-interaction of human Pex11pß during peroxisomal growth and division.

Pex11 proteins are involved in membrane elongation and division processes associated with the multiplication of peroxisomes. Human Pex11pß has recently been linked to a new disorder affecting peroxisome morphology and dynamics. Here, we have analyzed the exact membrane topology of Pex11pß. Studies with an epitope-specific antibody and protease protection assays show that Pex11pß is an integral membrane protein with two transmembrane domains flanking an internal region exposed to the peroxisomal matrix and N- and C-termini facing the cytosol. A glycine-rich internal region within Pex11pß is dispensable for peroxisome membrane elongation and division. However, we demonstrate that an amphipathic helix (Helix 2) within the first N-terminal 40 amino acids is crucial for membrane elongation and self-interaction of Pex11pß. Interestingly, we find that Pex11pß self-interaction strongly depends on the detergent used for solubilization. We also show that N-terminal cysteines are not essential for membrane elongation, and that putative N-terminal phosphorylation sites are dispensable for Pex11pß function. We propose that self-interaction of Pex11pß regulates its membrane deforming activity in conjunction with membrane lipids.

Postfixation detergent treatment liberates the membrane modelling protein Pex11ß from peroxisomal membranes.

Pex11 proteins are involved in membrane remodelling processes of peroxisomes, and are key components of peroxisomal division and proliferation. In mammals, three Pex11 isoforms, Pex11α, Pex11ß, and Pex11γ exist. Here we demonstrate that Pex11ß, but not Pex11α or Pex11γ, is almost exclusively extracted from peroxisomal membranes of paraformaldehyde-fixed cells by permeabilisation with the non-ionic detergent Triton X-100. This results in diminished detection of Myc-Pex11ß in immunofluorescence preparations and appearance of the protein in the Triton X-100 extract. To our knowledge, Pex11ß is the first peroxisomal membrane protein showing such a peculiar behaviour. Loss of Pex11ß can be avoided by permeabilisation with digitonin, the addition of glutaraldehyde to the fixative, or the expression of a Pex11 fusion protein with a larger protein tag (e.g. YFP). Our observations further point to different functions and biochemical properties of the Pex11 isoforms within the peroxisomal membrane and during peroxisome proliferation.

The peroxisome: an update on mysteries.

Peroxisomes contribute to several crucial metabolic processes such as ß-oxidation of fatty acids, biosynthesis of ether phospholipids and metabolism of reactive oxygen species, which render them indispensable to human health and development. Peroxisomes are highly dynamic organelles that rapidly assemble, multiply and degrade in response to metabolic needs. In recent years, the interest in peroxisomes and their physiological functions has significantly increased. This review intends to highlight recent discoveries and trends in peroxisome research, and represents an update as well as a continuation of a former review article. Novel exciting findings on the biological functions, biogenesis, formation and degradation of peroxisomes, on peroxisomal dynamics and division, as well as on the interaction and cross-talk of peroxisomes with other subcellular compartments are addressed. Furthermore, recent findings on the role of peroxisomes in the brain are discussed.

The functions of steryl glycosides come to those who wait: Recent advances in plants, fungi, bacteria and animals.

The attachment of a sugar moiety to the 3-hydroxy group of a sterol drastically increases the size of the hydrophilic part of the lipid. It is obvious that the glycosylation of a considerable fraction of membrane-bound free sterols alters the biophysical properties of the membrane. However, the consequences of such changes in the proportions of free sterols and steryl glycosides on the biological functions of a membrane are still unclear. This is the main hurdle in understanding the biological functions of steryl glycosides on a molecular level. The recent cloning of sterol glycosyltransferase genes from plants, fungi and bacteria has enabled genetic approaches to analyze steryl glycoside functions. Down regulation of phytosteryl beta-glycoside biosynthesis in Arabidopsis thaliana causes several dysfunctions in seed development. Ergosteryl beta-glycoside depleted mutants of the yeast Pichia pastoris lose their ability to degrade their peroxisomes by an autophagic mechanism called micropexophagy. In the plant-pathogenic fungus Colletotrichum orbiculare the same defect impairs invasion of the cucumber host plants. Helicobacter pylori, a bacterium colonizing the human stomach, is unable to modulate the host's immune response when the cholesteryl alpha-glycoside biosynthesis of the bacterium is mutated. These mutants with manipulated steryl glycoside metabolism will inspire further studies with cell biological, biophysical and other methods that will provide us with a mechanistic understanding of steryl glycoside functions.