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Journal ArticleDOI

Peroxisomes: flexible and dynamic organelles

01 Aug 2002-Current Opinion in Cell Biology (CURRENT BIOLOGY LTD)-Vol. 14, Iss: 4, pp 500-505
TL;DR: Peroxisome development is a dynamic process that may involve organelle fusion and fission events and includes a cycling receptor that passes the peroxisomal membrane.
About: This article is published in Current Opinion in Cell Biology.The article was published on 2002-08-01 and is currently open access. It has received 30 citations till now. The article focuses on the topics: Organelle fusion & Integral membrane protein.

Summary (2 min read)

Introduction

  • Peroxisomes are ubiquitous cell organelles that strongly vary in abundance and function between cells.
  • Characteristic is their extremely high matrix-protein concentration, sometimes leading to crystalline inclusions.
  • The matrix is packed with enzyme molecules that catalyse diverse oxidative and biosynthetic reactions [1,2].
  • Their identification is severely hampered by the exceptionally low abundance of peroxisomal membrane proteins (PMPs) [4].
  • Recent breakthroughs in this fascinating field are discussed in this paper.

Peroxisome development

  • The prevailing model of peroxisome biogenesis, proposed by Lazarow and Fujiki in 1985 [6], predicts that the organelle grows by uptake of new components from the cytosol and multiplies by division .
  • Most PMPs, however, are thought to be sorted directly to the peroxisomal membrane [7].
  • Different mPTSs — targeting signals of PMPs — have been identified [7].
  • Mutational analysis of the mPTS region of Hansenula polymorpha Pex3p revealed that only part of these charges are essential for targeting, however [9].
  • Three peroxins (Pex3p, Pex16p and Pex19p) have been implicated in PMP targeting/insertion [10–12].

Matrix protein import

  • For matrix proteins, two peroxisomal targeting signals (PTS1 and PTS2) are known that are recognised by the cytosolic receptors Pex5p and Pex7p, respectively.
  • Pex8p, Pex12p, Pex13p and Pex14p interact with the amino-terminal half of Pex5p.
  • Instead, they may reflect differences in experimental approaches.
  • Hypothetical models on PTS1 protein import generally propose a single import pathway.
  • This model predicts that newly synthesized peroxisomal matrix proteins (MPs) and membrane proteins (PMPs) are incorporated in pre-existing, nascent peroxisomes (NP).

Peroxisome division

  • Two proteins, Pex11p and VPS1, have been proposed to function in peroxisome fission.
  • Alternatively, Pex11p molecules might be involved in a coat-mediated budding process.
  • These structures harbour distinct subsets of membrane proteins, as well as components of coat protein II vesicles, and transform into early peroxisomal precursors, designated P1 and P2, as a result of the uptake of additional membrane proteins and release of the elements.
  • In peroxisome-deficient human fibroblasts also, evidence was obtained for a multistep peroxisome-assembly pathway to form new peroxisomes upon reintroduction of PEX16 into cells of a Pex16p-defective cell line [12] .
  • The Y. lipolytica model proposes that this pathway occurs in wild-type cells upon induction of peroxisome formation.

Conclusions

  • Their knowledge on their precise function is still remarkably poor.
  • As outlined by Purdue and Lazarow [7] for the highly diverse functions suggested for Pex1p and Pex6p (vesicle fusion versus matrix-protein import), it is difficult to envisage that these discrepancies are simply due to species differences or are methodology related.
  • Especially for yeasts the physiology (growth conditions, substrates, growth phase) of the examined cells may differ largely.
  • Obviously, these variations are reflected in cell performance and thus also in the kinetics of processes involved in peroxisome biogenesis.
  • The use of normalised cells also seems crucial for comparison of data of future genomic/proteomic approaches.

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Citations
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Journal ArticleDOI
TL;DR: It is concluded that Pex8p organizes the formation of the larger import complex from the trans side of the peroxisomal membrane and thus might enable functional communication between both sides of the membrane.

236 citations

Journal ArticleDOI
TL;DR: ROS cannot be perceived anymore as a mere harmful consequence of external factors, or byproducts of altered cellular metabolism, so the indiscriminate use of anti-oxidants did not produce the expected “beneficial” results in many medical applications attempted so far, underlying the need for a deeper apprehension of the biological roles of ROS, particularly in the context of the higher cellular order of organelles.
Abstract: The presence and supposed roles of reactive oxygen species (ROS) were reported in literature in a myriad of instances. However, the breadth and depth of their involvement in cellular physiology and pathology, as well as their relationship to the redox environment can only be guessed from specialized reports. Whatever their circumstances of formation or consequences, ROS seem to be conspicuous components of intracellular milieu. We sought to verify this assertion, by collecting the available evidence derived from the most recent publications in the biomedical field. Unlike other reviews with similar objectives, we centered our analysis on the subcellular compartments, namely on organelles, grouped according to their major functions. Thus, plasma membrane is a major source of ROS through NAD(P)H oxidases located on either side. Enzymes of the same class displaying low activity, as well as their components, are also present free in cytoplasm, regulating the actin cytoskeleton and cell motility. Mitochondria can be a major source of ROS, mainly in processes leading to apoptosis. The protein synthetic pathway (endoplasmic reticulum and Golgi apparatus), including the nucleus, as well as protein turnover, are all exquisitely sensitive to ROS-related redox conditions. The same applies to the degradation pathways represented by lysosomes and peroxisomes. Therefore, ROS cannot be perceived anymore as a mere harmful consequence of external factors, or byproducts of altered cellular metabolism. This may explain why the indiscriminate use of anti-oxidants did not produce the expected "beneficial" results in many medical applications attempted so far, underlying the need for a deeper apprehension of the biological roles of ROS, particularly in the context of the higher cellular order of organelles.

184 citations


Cites background from "Peroxisomes: flexible and dynamic o..."

  • ...…genetic defects, or the role of peroxisome proliferators and their receptors in the control of peroxisome functions and fate, for there are many available reviews (Brown and Baker 2003; Masters 1996; Masters and Crane 1995a; Michalik et al. 2004; Singh 1996, 1997; van der Klei and Veenhuis 2002)....

    [...]

Journal ArticleDOI
TL;DR: The structure of the receptor/cargo complex demonstrates that the primary receptor-binding site of the cargo is structurally and topologically autonomous, enabling the cargo to retain its native structure and function.

161 citations


Cites background from "Peroxisomes: flexible and dynamic o..."

  • ...Peroxisomal import is one of the few transport processes that uses a translocon for the purpose of trafficking folded and functional cargo proteins across membranes (Gould and Collins, 2002; Holroyd and Erdmann, 2001; Lazarow, 2003; Schnell, 2000; van der Klei and Veenhuis, 2002)....

    [...]

Journal ArticleDOI
TL;DR: This review addresses the current state of knowledge concerning the dynamics and fission of peroxisomes, especially in relation to mitochondrial morphology and division in mammalian cells.

140 citations

Journal ArticleDOI
TL;DR: It is demonstrated that Cta1p can also enter mitochondria, although the enzyme lacks a classical mitochondrial import sequence and presumably functions as scavenger of H2O2 and mitochondrial-derived ROS.
Abstract: Yeast catalase A (Cta1p) contains two peroxisomal targeting signals (SSNSKF) localized at its C-terminus and within the N-terminal third of the protein, which both can target foreign proteins to peroxisomes. In the present study we demonstrated that Cta1p can also enter mitochondria, although the enzyme lacks a classical mitochondrial import sequence. Cta1p co-targeting was studied in a catalase A null mutant after growth on different carbon sources, and expression of a Cta1p-GFP (green fluorescent protein)-fusion protein or a Cta1p derivative containing either a c-Myc epitope (Cta1p(myc)) or a SKF-extended tag (Cta1p(myc-SKF)). Peroxisomal and mitochondrial co-import of catalase A were tested qualitatively by fluorescence microscopy and functional complementation of a Delta cta1 null mutation, and quantitatively by subcellular fractionation followed by Western blot analysis and enzyme activity assays. Efficient Cta1p import into peroxisomes was observed when cells were cultivated under peroxisome-inducing conditions (i.e. growth on oleate), whereas significant co-import of Cta1p-GFP into mitochondria occurred when cells were grown under respiratory conditions that favour oxygen stress and ROS (reactive oxygen species) accumulation within this organelle. In particular, when cells were grown on the non-fermentable carbon source raffinose, respiration is maximally enhanced, and catalase A was efficiently targeted to the mitochondrial matrix where it presumably functions as scavenger of H2O2 and mitochondrial-derived ROS.

125 citations

References
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Journal ArticleDOI

1,112 citations

Journal ArticleDOI
TL;DR: The crystal structure of a fragment of human PEX5 that includes all seven predicted TPR motifs in complex with a pentapeptide containing a PTS1 sequence is reported, revealing the molecular basis for PTS1 recognition and demonstrating a novel mode of TPR–peptide interaction.
Abstract: Many proteins contain targeting signals within their sequences that specify their delivery to particular organelles. The peroxisomal targeting signal-1 (PTS1) is a C-terminal tripeptide that is sufficient to direct proteins into peroxisomes. The PTS1 sequence closely approximates Ser-Lys-Leu-COO-. PEX5, the receptor for PTS1, interacts with the signal via a series of tetratricopeptide repeats (TPRs) within its C-terminal half. Here we report the crystal structure of a fragment of human PEX5 that includes all seven predicted TPR motifs in complex with a pentapeptide containing a PTS1 sequence. Two clusters of three TPRs almost completely surround the peptide, while a hinge region, previously identified as TPR4, forms a distinct structure that enables the two sets of TPRs to form a single binding site. This structure reveals the molecular basis for PTS1 recognition and demonstrates a novel mode of TPR-peptide interaction.

363 citations

Journal ArticleDOI
TL;DR: Altered distribution or stability of the PTS1 receptor in all cells with a defect in PTS1 protein import implies that the genes mutated in these cell lines encode proteins with a direct role in peroxisomal protein import.
Abstract: PEX5 encodes the type-1 peroxisomal targeting signal (PTS1) receptor, one of at least 15 peroxins required for peroxisome biogenesis. Pex5p has a bimodal distribution within the cell, mostly cytosolic with a small amount bound to peroxisomes. This distribution indicates that Pex5p may function as a cycling receptor, a mode of action likely to require interaction with additional peroxins. Loss of peroxins required for protein translocation into the peroxisome (PEX2 or PEX12) resulted in accumulation of Pex5p at docking sites on the peroxisome surface. Pex5p also accumulated on peroxisomes in normal cells under conditions which inhibit protein translocation into peroxisomes (low temperature or ATP depletion), returned to the cytoplasm when translocation was restored, and reaccumulated on peroxisomes when translocation was again inhibited. Translocation inhibiting conditions did not result in Pex5p redistribution in cells that lack detectable peroxisomes. Thus, it appears that Pex5p can cycle repeatedly between the cytoplasm and peroxisome. Altered activity of the peroxin defective in CG7 cells leads to accumulation of Pex5p within the peroxisome, indicating that Pex5p may actually enter the peroxisome lumen at one point in its cycle. In addition, we found that the PTS1 receptor was extremely unstable in the peroxin-deficient CG1, CG4, and CG8 cells. Altered distribution or stability of the PTS1 receptor in all cells with a defect in PTS1 protein import implies that the genes mutated in these cell lines encode proteins with a direct role in peroxisomal protein import.

314 citations

Journal ArticleDOI
TL;DR: Pmp27p, the most abundant peroxisomal membrane from Saccharomyces cerevisiae, was purified and the corresponding gene PMP27 was cloned and sequenced, suggesting that PMP27p may be involved in parceling of peroxISomes into regular quanta.
Abstract: We have purified peroxisomal membranes from Saccharomyces cerevisiae after induction of peroxisomes in oleic acid-containing media. About 30 distinct proteins could be discerned among the HPLC- and SDS-PAGE-separated proteins of the high salt-extracted peroxisomal membranes. The most abundant of these, Pmp27p, was purified and the corresponding gene PMP27 was cloned and sequenced. Its primary structure is 32% identical to PMP31 and PMP32 of the yeast Candida biodinii (Moreno, M., R. Lark, K. L. Campbell, and M. J. Goodman. 1994. Yeast. 10:1447-1457). Immunoelectron microscopic localization of Pmp27p showed labeling of the peroxisomal membrane, but also of matrix-less and matrix containing tubular membranes nearby. Electronmicroscopical data suggest that some of these tubular extensions might interconnect peroxisomes to form a peroxisomal reticulum. Cells with a disrupted PMP27 gene (delta pmp27) still grew well on glucose or ethanol, but they failed to grow on oleate although peroxisomes were still induced by transfer to oleate-containing media. The induced peroxisomes of delta pmp27 cells were fewer but considerably larger than those of wild-type cells, suggesting that Pmp27p may be involved in parceling of peroxisomes into regular quanta. delta pmp27 cells cultured in oleate-containing media form multiple buds, of which virtually all are peroxisome deficient. The growth defect of delta pmp27 cells on oleic acid appears to result from the inability to segregate the giant peroxisomes to daughter cells.

300 citations

Frequently Asked Questions (1)
Q1. What are the contributions in this paper?

In this paper, the peroxisomal membrane proteins ( PMPs ) have been identified and their functional properties have been investigated.