Pexophagy-linked degradation of the peroxisomal membrane protein Pex3p involves the ubiquitin–proteasome system

Williams, Chris; Klei, Ida J. van der

doi:10.1016/j.bbrc.2013.07.086

Cited by 29 publications

(13 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This could be used to probe the translocation mechanism of peroxisomal matrix proteins in yeast. Nevertheless, the role of peroxisomal ubiquitin in pexophagy appears to be, at best, indirect in yeast [10], [64]–[66] so that our discussion of ubiquitin thresholds and pexophagy is restricted to mammalian systems.…”

Section: Resultsmentioning

confidence: 99%

PEX5 and Ubiquitin Dynamics on Mammalian Peroxisome Membranes

2014

View full text Add to dashboard Cite

Peroxisomes are membrane-bound organelles within eukaryotic cells that post-translationally import folded proteins into their matrix. Matrix protein import requires a shuttle receptor protein, usually PEX5, that cycles through docking with the peroxisomal membrane, ubiquitination, and export back into the cytosol followed by deubiquitination. Matrix proteins associate with PEX5 in the cytosol and are translocated into the peroxisome lumen during the PEX5 cycle. This cargo translocation step is not well understood, and its energetics remain controversial. We use stochastic computational models to explore different ways the AAA ATPase driven removal of PEX5 may couple with cargo translocation in peroxisomal importers of mammalian cells. The first model considered is uncoupled, in which translocation is spontaneous, and does not immediately depend on PEX5 removal. The second is directly coupled, in which cargo translocation only occurs when its PEX5 is removed from the peroxisomal membrane. The third, novel, model is cooperatively coupled and requires two PEX5 on a given importomer for cargo translocation — one PEX5 with associated cargo and one with ubiquitin. We measure both the PEX5 and the ubiquitin levels on the peroxisomes as we vary the matrix protein cargo addition rate into the cytosol. We find that both uncoupled and directly coupled translocation behave identically with respect to PEX5 and ubiquitin, and the peroxisomal ubiquitin signal increases as the matrix protein traffic increases. In contrast, cooperatively coupled translocation behaves dramatically differently, with a ubiquitin signal that decreases with increasing matrix protein traffic. Recent work has shown that ubiquitin on mammalian peroxisome membranes can lead to selective degradation by autophagy, or ‘pexophagy.’ Therefore, the high ubiquitin level for low matrix cargo traffic with cooperatively coupled protein translocation could be used as a disuse signal to mediate pexophagy. This mechanism may be one way that cells could regulate peroxisome numbers.

show abstract

Section: Resultsmentioning

confidence: 99%

PEX5 and Ubiquitin Dynamics on Mammalian Peroxisome Membranes

2014

View full text Add to dashboard Cite

show abstract

“…Protein ubiquitination has been shown to influence peroxisome protein import and autophagy by targeting Pex5: mono-ubiquitination at Cys11 leads to recycling of the PTS1-import receptor from the peroxisomal membrane back into the cytosol whilst poly-ubiquitination marks peroxisomes for degradation by autophagy [42]. In addition, ubiquitination of other peroxins has been described to influence protein import and degradation of peroxisomes [56,95,184,188] (see Chapter by Platta & Eggeling, this issue). Interestingly, the ubiquitinatable Cys11/10 of Pex5 was shown to be redox-sensitive in humans and P. pastoris [98,113].…”

Section: Kinases and Phosphatases In Peroxisome Biogenesis And Metabomentioning

confidence: 94%

Proliferation and fission of peroxisomes — An update

Schrader

Costello

Godinho

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

124

142

View full text Add to dashboard Cite

In mammals, peroxisomes perform crucial functions in cellular metabolism, signalling and viral defense which are essential to the health and viability of the organism. In order to achieve this functional versatility peroxisomes dynamically respond to molecular cues triggered by changes in the cellular environment. Such changes elicit a corresponding response in peroxisomes, which manifests itself as a change in peroxisome number, altered enzyme levels and adaptations to the peroxisomal structure. In mammals the generation of new peroxisomes is a complex process which has clear analogies to mitochondria, with both sharing the same division machinery and undergoing a similar division process. How the regulation of this division process is integrated into the cell's response to different stimuli, the signalling pathways and factors involved, remains somewhat unclear. Here, we discuss the mechanism of peroxisomal fission, the contributions of the various division factors and examine the potential impact of post-translational modifications, such as phosphorylation, on the proliferation process. We also summarize the signalling process and highlight the most recent data linking signalling pathways with peroxisome proliferation.

show abstract

“…Both receptors physically interact with Atg11 . Interestingly, Pex3 has a different role in H. polymorpha pexophagy, where initiation of pexophagy requires the removal of Pex3 via the ubiquitin proteasome pathway . In mammalian cells, PEX3 has also been implicated in pexophagy .…”

Section: Alternative Functions Of Pex3 and Pex19mentioning

confidence: 99%

The peroxisome biogenesis factors Pex3 and Pex19: multitasking proteins with disputed functions

Jansen

Klei

2019

FEBS Letters

View full text Add to dashboard Cite

The peroxisomal membrane protein (PMP) Pex3 and its cytosolic interaction partner Pex19 have been implicated in peroxisomal membrane biogenesis. Although these peroxins have been extensively studied, no consensus has been reached yet on how they operate. Here, we discuss two major models of their function, namely, in direct insertion of proteins into the peroxisomal membrane or in formation of PMP‐containing vesicles from the endoplasmic reticulum (ER). Pex3 can also recruit other proteins to the peroxisomal membrane (e.g., Inp1, Atg30, Atg36), thereby fulfilling roles in other processes such as autophagy and organelle retention. Recent studies indicate that Pex3 and Pex19 can also facilitate sorting of certain membrane proteins to other cellular organelles, including the ER, lipid droplets, and mitochondria.

show abstract

Pexophagy-linked degradation of the peroxisomal membrane protein Pex3p involves the ubiquitin–proteasome system

Cited by 29 publications

References 44 publications

PEX5 and Ubiquitin Dynamics on Mammalian Peroxisome Membranes

PEX5 and Ubiquitin Dynamics on Mammalian Peroxisome Membranes

Proliferation and fission of peroxisomes — An update

The peroxisome biogenesis factors Pex3 and Pex19: multitasking proteins with disputed functions

Contact Info

Product

Resources

About