Role of AAA + -proteins in peroxisome biogenesis and function

Grimm, Immanuel; Erdmann, Ralf; Girzalsky, Wolfgang

doi:10.1016/j.bbamcr.2015.10.001

Cited by 16 publications

(18 citation statements)

References 152 publications

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“…Analysis of peroxisome‐defective mutants from a variety of organisms indicates that import of peroxisomal matrix protein requires recycling of PEX5 by the peroxisomal ATPase complex (reviewed in Grimm et al ., ; Figure a). Like human pex6 patient‐derived cell lines (Dodt and Gould, ), Arabidopsis pex6‐1 has low PEX5 levels (Zolman and Bartel, ), probably because PEX5 accumulating in the membrane (Ratzel et al ., ) in the absence of efficient retrotranslocation is degraded by the proteasome (Kao and Bartel, ) rather than recycled.…”

Section: Discussionmentioning

confidence: 99%

“…After PEX5 ubiquitination, the peroxisome-associated ATPases, PEX1 and PEX6, retrotranslocate PEX5 from the membrane back to the cytosol (reviewed in Grimm et al, 2016). PEX1 and PEX6 are members of a family of AAA proteins (ATPases associated with various cellular activities) with two AAA domains, AAA1 and AAA2.…”

Section: Introductionmentioning

confidence: 99%

“…Unlike most AAA proteins, which are homohexamers, yeast PEX1 and PEX6 form a heterohexamer (Saffian et al, 2012) of alternating subunits arranged as a trimer of dimers (Blok et al, 2015;Ciniawsky et al, 2015;Gardner et al, 2015). Although AAA domains generally contain Walker A and B motifs involved in ATP-binding and hydrolysis, respectively (reviewed in Grimm et al, 2016), PEX1 and PEX6 lack canonical Walker B motifs in AAA1, rendering AAA1 unable to hydrolyze ATP (reviewed in Grimm et al, 2016). However, ATP binding by the Walker A motif in yeast PEX1 AAA1 is required for interaction of PEX1 and PEX6 in vitro (Gardner et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Disparate peroxisome‐related defects in Arabidopsis pex6 and pex26 mutants link peroxisomal retrotranslocation and oil body utilization

et al. 2017

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SUMMARY Catabolism of fatty acids stored in oil bodies is essential for Arabidopsis seed germination and seedling development. This fatty acid breakdown occurs in peroxisomes, organelles that sequester oxidative reactions. Import of peroxisomal enzymes is facilitated by peroxins including PEX5, a receptor that delivers cargo proteins from the cytosol to the peroxisomal matrix. After cargo delivery, a complex of the PEX1 and PEX6 ATPases and the PEX26 tail-anchored membrane protein removes ubiquitinated PEX5 from the peroxisomal membrane. We identified Arabidopsis pex6 and pex26 mutants by screening for inefficient seedling β-oxidation phenotypes. The mutants displayed distinct defects in growth, response to a peroxisomally metabolized auxin precursor, and peroxisomal protein import. The low PEX5 levels in these mutants were increased by proteasome inhibitor treatment or by combining pex26 with peroxisome-associated ubiquitination machinery mutants, suggesting that ubiquitinated PEX5 is degraded by the proteasome when PEX6 or PEX26 function is reduced. Combining pex26 with mutations that increase PEX5 levels either worsened or improved pex26 physiological and molecular defects, depending on the introduced lesion. Moreover, elevating PEX5 levels via a 35S:PEX5 transgene exacerbated pex26 defects and ameliorated the defects of only a subset of pex6 alleles, implying that decreased PEX5 is not the sole molecular deficiency in these mutants. We found peroxisomes clustered around persisting oil bodies in pex6 and pex26 seedlings, suggesting a role for peroxisomal retrotranslocation machinery in oil body utilization. The disparate phenotypes of these pex alleles may reflect unanticipated functions of the peroxisomal ATPase complex.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Disparate peroxisome‐related defects in Arabidopsis pex6 and pex26 mutants link peroxisomal retrotranslocation and oil body utilization

et al. 2017

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“…68 They interact with each other in the presence of ATP and are both required for peroxisome biogenesis. 69 PEX15, PEX26, and APM9 have been identified as peroxisomal membrane anchors for PEX6 in yeast, 70 mammalian cells, 71 and plants 72 respectively. These anchor proteins recruit the PEX1-PEX6 complex to peroxisome membranes ( Figure 1A, C).…”

Section: Role Of Pex5 Ubiquitination In Peroxisome Biogenesismentioning

confidence: 99%

Role of PEX5 ubiquitination in maintaining peroxisome dynamics and homeostasis

Wang

Subramani

2017

Cell Cycle

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Peroxisomes are essential and dynamic organelles that allow cells to rapidly adapt and cope with changing environments and/or physiological conditions by modulation of both peroxisome biogenesis and turnover. Peroxisome biogenesis involves the assembly of peroxisome membranes and the import of peroxisomal matrix proteins. The latter depends on the receptor, PEX5, which recognizes peroxisomal matrix proteins in the cytosol directly or indirectly, and transports them to the peroxisomal lumen. In this review, we discuss the role of PEX5 ubiquitination in both peroxisome biogenesis and turnover, specifically in PEX5 receptor recycling, stability and abundance, as well as its role in pexophagy (autophagic degradation of peroxisomes).

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“…Like all hexameric AAA+ ATPases p97 features a central cavity or pore lined by putative substrate interacting loops. Further members belonging to this group, referred to as NSF/Cdc48/Pex family, are the N-ethylmaleimide-sensitive fusion protein (NSF) involved in vesicular transport processes (reviewed in Zhao and Brunger, 2016), SPATA5 (spermatogenesis associated 5) and NVL (nuclear VCP-like) (Drg1 and Rix7 in yeast) involved in ribosome biogenesis (reviewed in Kressler et al, 2012) as well as PEX1 and PEX6 involved in peroxisome biogenesis (reviewed in Grimm et al, 2016). A feature unique to p97 is its 76 amino acid long, unstructured C-terminal extension, which is highly flexible and is involved in the regulation of the ATPase activity and cofactor assembly, the latter being modulated by phosphorylation (Li et al, 2008; Ewens et al, 2010; Niwa et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

The Interplay of Cofactor Interactions and Post-translational Modifications in the Regulation of the AAA+ ATPase p97

Hänzelmann

Schindelin

2017

Front. Mol. Biosci.

129

134

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The hexameric type II AAA ATPase (ATPase associated with various activities) p97 (also referred to as VCP, Cdc48, and Ter94) is critically involved in a variety of cellular activities including pathways such as DNA replication and repair which both involve chromatin remodeling, and is a key player in various protein quality control pathways mediated by the ubiquitin proteasome system as well as autophagy. Correspondingly, p97 has been linked to various pathophysiological states including cancer, neurodegeneration, and premature aging. p97 encompasses an N-terminal domain, two highly conserved ATPase domains and an unstructured C-terminal tail. This enzyme hydrolyzes ATP and utilizes the resulting energy to extract or disassemble protein targets modified with ubiquitin from stable protein assemblies, chromatin and membranes. p97 participates in highly diverse cellular processes and hence its activity is tightly controlled. This is achieved by multiple regulatory cofactors, which either associate with the N-terminal domain or interact with the extreme C-terminus via distinct binding elements and target p97 to specific cellular pathways, sometimes requiring the simultaneous association with more than one cofactor. Most cofactors are recruited to p97 through conserved binding motifs/domains and assist in substrate recognition or processing by providing additional molecular properties. A tight control of p97 cofactor specificity and diversity as well as the assembly of higher-order p97-cofactor complexes is accomplished by various regulatory mechanisms, which include bipartite binding, binding site competition, changes in oligomeric assemblies, and nucleotide-induced conformational changes. Furthermore, post-translational modifications (PTMs) like acetylation, palmitoylation, phosphorylation, SUMOylation, and ubiquitylation of p97 have been reported which further modulate its diverse molecular activities. In this review, we will describe the molecular basis of p97-cofactor specificity/diversity and will discuss how PTMs can modulate p97-cofactor interactions and affect the physiological and patho-physiological functions of p97.

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Role of AAA + -proteins in peroxisome biogenesis and function

Cited by 16 publications

References 152 publications

Disparate peroxisome‐related defects in Arabidopsis pex6 and pex26 mutants link peroxisomal retrotranslocation and oil body utilization

Disparate peroxisome‐related defects in Arabidopsis pex6 and pex26 mutants link peroxisomal retrotranslocation and oil body utilization

Role of PEX5 ubiquitination in maintaining peroxisome dynamics and homeostasis

The Interplay of Cofactor Interactions and Post-translational Modifications in the Regulation of the AAA+ ATPase p97

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