Targeting of Pex8p to the peroxisomal importomer

Deckers, Markus; Emmrich, Kerstin; Girzalsky, Wolfgang; Awa, Wendy L.; Kunau, Wolf‐H.; Erdmann, Ralf

doi:10.1016/j.ejcb.2010.06.019

Cited by 12 publications

(5 citation statements)

References 56 publications

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“…Cargo-bound Pex5 docks to its peroxisome membrane receptors, Pex13 and Pex14, to deliver cargo across the membrane by forming a pore-like structure called the docking/translocation module (DTM) [65][66][67][68][69] (Figure 1B). The minimal and actual DTM composition depends on the substrate and possibly the stage of import [70][71][72][73][74], but it typically comprises a heterooligomer of Pex5, Pex13, and Pex14 (with Pex17 in yeast) that changes in size depending on the size of the cargo [65]. Pex5's N-terminal domain binds N-and C-terminal domains of Pex14 [66,75,76] and a C-terminal SH3 domain in Pex13 [68,77].…”

Section: Matrix Protein Importmentioning

confidence: 99%

Insights into the Structure and Function of the Pex1/Pex6 AAA-ATPase in Peroxisome Homeostasis

Judy

Sheedy

Gardner

2022

Cells

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The AAA-ATPases Pex1 and Pex6 are required for the formation and maintenance of peroxisomes, membrane-bound organelles that harbor enzymes for specialized metabolism. Together, Pex1 and Pex6 form a heterohexameric AAA-ATPase capable of unfolding substrate proteins via processive threading through a central pore. Here, we review the proposed roles for Pex1/Pex6 in peroxisome biogenesis and degradation, discussing how the unfolding of potential substrates contributes to peroxisome homeostasis. We also consider how advances in cryo-EM, computational structure prediction, and mechanisms of related ATPases are improving our understanding of how Pex1/Pex6 converts ATP hydrolysis into mechanical force. Since mutations in PEX1 and PEX6 cause the majority of known cases of peroxisome biogenesis disorders such as Zellweger syndrome, insights into Pex1/Pex6 structure and function are important for understanding peroxisomes in human health and disease.

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Section: Matrix Protein Importmentioning

confidence: 99%

Insights into the Structure and Function of the Pex1/Pex6 AAA-ATPase in Peroxisome Homeostasis

Judy

Sheedy

Gardner

2022

Cells

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“…Similar to H. polymorpha ( 34 ), we found that PEX14, PEX8, and PEX5 were also required to maintain low levels of PEX13, although apparently with a higher impact for PEX5 and PEX14 in P. anserina . In budding yeast, Pex13 interacts with both Pex14 and Pex8, while Pex8 bridges the docking peroxins to the RING-finger complex ( 39 , 54 ). Therefore, in line with a ubiquitination-dependent regulation of PEX13 protein levels, delivery of PEX13 to the ubiquitination complex could depend on these interactions.…”

Section: Discussionmentioning

confidence: 99%

The peroxisome protein translocation machinery is developmentally regulated in the fungus Podospora anserina

Aguirre-López,

Suaste-Olmos,

Peraza-Reyes

2024

Microbiol Spectr

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Peroxisomes are versatile organelles that are essential for diverse developmental processes. Peroxisome function critically depends on its matrix proteins, which are imported from the cytosol by the receptors Pex5 and Pex7. These receptors cycle into and out of peroxisomes through two membrane protein channels. Cargo-loaded Pex5 is imported into peroxisomes through the docking/translocation machinery, which is composed of Pex13 and Pex14. After cargo delivery, Pex5 is exported through the peroxisome ubiquitin ligase complex. This complex also ubiquitinates the receptors dictating their membrane extraction by the peroxisome AAA ATPase complex. In the fungus Podospora anserina, peroxisomes are required for meiotic induction. This process relies on PEX13 but not on PEX14. In addition, PEX14 is partially dispensable for peroxisome protein import during meiotic development, suggesting a developmental regulation of the translocation machinery. Here we show that PEX13 abundance in hyphae is maintained at low levels by the activity of the peroxisome ubiquitin ligase complex and the ubiquitin-conjugating enzyme PEX4, in conjunction with PEX14, PEX5, and with the peroxin that bridges the ubiquitination and the docking/translocation machineries, PEX8. Moreover, we found that the AAA ATPase complex and the peroxins that drive peroxisome membrane formation—PEX3 and PEX19—are also required to restrain PEX13 levels and that in their absence PEX13 associates with mitochondria. Furthermore, we found that PEX13 levels are higher throughout sexual development, where they are further increased during meiocyte and meiotic-spore differentiation. Our findings show that the peroxisome protein translocation machinery is subject to complex developmental regulation, which finely modulates PEX13 along sexual development. IMPORTANCE Sexual reproduction allows eukaryotic organisms to produce genetically diverse progeny. This process relies on meiosis, a reductional division that enables ploidy maintenance and genetic recombination. Meiotic differentiation also involves the renewal of cell functioning to promote offspring rejuvenation. Research in the model fungus Podospora anserina has shown that this process involves a complex regulation of the function and dynamics of different organelles, including peroxisomes. These organelles are critical for meiosis induction and play further significant roles in meiotic development. Here we show that PEX13—a key constituent of the protein conduit through which the proteins defining peroxisome function reach into the organelle—is subject to a developmental regulation that almost certainly involves its selective ubiquitination-dependent removal and that modulates its abundance throughout meiotic development and at different sexual differentiation processes. Our results show that meiotic development involves a complex developmental regulation of the peroxisome protein translocation system.

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“…In S. cerevisiae, Pex8 is located at the inner surface of the peroxisomal membrane and is essential for the assembly of the importomer (Deckers et al, 2010). Acetyl-CoA, one of the key buildings block for the synthesis of polyketides, can be produced via various catabolic pathways, including peroxisomal β-oxidation of fatty acids (Maggio-Hall et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Fusarium verticillioidesFvPex8 is a key component of peroxisomal docking/translocation module that serves important roles in fumonisin biosynthesis but not in virulence

Lin

Peng

Huang

et al. 2020

Preprint

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24Peroxisomes are ubiquitous organelles in eukaryotic cells that fulfill a variety of important 25 metabolic functions. In this study, we investigated the role of Docking/Translocation Module 26 (DTM) peroxins, mainly FvPex8, FvPex13, FvPex14, and FvPex33, in Fusarium verticillioides 27 virulence and fumonisin B1 (FB1) biosynthesis. Protein interaction experiments suggested that 28 FvPex13 serves as the core subunit of F. verticillioides DTM. When we generated gene deletion 29 mutants (ΔFvpex8, ΔFvpex13, ΔFvpex14, ΔFvpex33, ΔFvpex33/14) and examined whether the 30 expression of other peroxin genes were affected in the DTM mutants, ΔFvpex8 strain showed most 31 drastic changes to PEX gene expression profiles. When we tested other physiological changes in 32 these mutants, we observed disparity in carbon source utilization, especially sucrose and butyrate, 33 as well as unsaturated fatty acids oleic acid and linoleic acid. Deletion mutants exhibited defect in 34 cell wall integrity when stress agents were applied. The mutants also showed higher levels of lipid 35 droplet accumulation when compared to WT, particularly under nutrient starvation. Notably, 36ΔFvpex8 mutant showed significant FB1 reduction and altered expression of FUM1 (polyketide 37 synthase) and FUM19 (ABC transporter) genes. However, FvPex13 was primarily responsible for 38 virulence when tested on maize stalks, while ΔFvpex33/14 double mutant also showed virulence 39 defect. In summary, our study suggests that FvPex13 is the core component of F. verticillioides 40 DTM, regulating peroxisome membrane biogenesis as well as PTS1-and PTS2-mediated 41 transmembrane cargo transportation. However, FvPex8 is predicted to serve as a key component 42 in DTM that affects peroxisome function in β-oxidation and FB1 biosynthesis in F. verticillioides. 43 44

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Targeting of Pex8p to the peroxisomal importomer

Cited by 12 publications

References 56 publications

Insights into the Structure and Function of the Pex1/Pex6 AAA-ATPase in Peroxisome Homeostasis

Insights into the Structure and Function of the Pex1/Pex6 AAA-ATPase in Peroxisome Homeostasis

The peroxisome protein translocation machinery is developmentally regulated in the fungus Podospora anserina

Fusarium verticillioidesFvPex8 is a key component of peroxisomal docking/translocation module that serves important roles in fumonisin biosynthesis but not in virulence

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