Role of PEX5 ubiquitination in maintaining peroxisome dynamics and homeostasis

Wang, Wei; Subramani, Suresh

doi:10.1080/15384101.2017.1376149

Cited by 47 publications

(45 citation statements)

References 111 publications

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“…We recently revealed an indispensable role of TRIM37 in peroxisome biogenesis and the defective import of peroxisomal matrix proteins in cells depleted of TRIM37 [12]. As peroxisomes are involved in maintaining homeostasis of reactive oxygen species (ROS) [39,40] and recent papers show that oxidative stress modulates TFEB activation and MTORC1 activity via the lysosomal ROS sensor, MCOLN1/TRPML1 (mucolipin 1) [41,42], it seemed plausible that the potential disruption in ROS homeostasis mediates MTORC1 inhibition in TRIM37-deficient cells. To test this, we first examined ROS levels by using the DHR123 and CellRox dyes and found the ROS level in TRIM37 KD cells was comparable to those seen in control cells ( Fig.…”

Section: Trim37 Interacts With Mtor and Rragb And Its Depletion Inhibmentioning

confidence: 99%

TRIM37 deficiency induces autophagy through deregulating the MTORC1-TFEB axis

et al. 2018

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ACTB: actin beta; ATG: autophagy related; CASP3: caspase3; CLEAR: coordinated lysosomal expression and regulation; CQ: chloroquine; CTS: cathepsin proteases; CTSL: cathepsin L; EIF4EBP1: eukaryotic translation initiation factor 4E binding protein 1; LAMP1: lysosomal associated membrane protein 1; LAMP2: lysosomal associated membrane protein 2; LMNB1: lamin B1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; mulibrey: muscle-liver-brain-eye; NAC: N-acetyl-L-cysteine; PARP1: poly(ADP-ribose) polymerase 1; RAP2A: member of RAS oncogene family; RHEB: Ras homolog enriched in brain; ROS: reactive oxygen species; RPS6KB1: ribosomal protein S6 kinase B1; RRAGB: Ras related GTP binding B; SQSTM1: sequestosome 1; TFEB: transcription factor EB; TRIM37: tripartite motif containing 37.

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Section: Trim37 Interacts With Mtor and Rragb And Its Depletion Inhibmentioning

confidence: 99%

TRIM37 deficiency induces autophagy through deregulating the MTORC1-TFEB axis

et al. 2018

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“…The best established role concerns its requirement for peroxisomal matrix protein import [5]. Functional analysis in yeast and mammalian cells revealed that the AAA complex functions as dislocase for the ubiquitinated PTS1 (peroxisomal targeting signal type 1)-import receptor Pex5, enabling further rounds of PTS1-import [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

“…The occurrence and functional role of the different Ub-modifications of Pex5 are conserved from yeast to man. According to the published data from different organisms, the AAA-dependent removal of the unloaded Ub-Pex5 is thought to generate room for newly incoming cargo-bound Pex5 molecules, as the binding capacities at the peroxisomal membrane seem to be limited [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

The Peroxisomal PTS1-Import Defect of PEX1- Deficient Cells Is Independent of Pexophagy in Saccharomyces cerevisiae

Mastalski

Brinkmeier

Platta

2020

IJMS

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The important physiologic role of peroxisomes is shown by the occurrence of peroxisomal biogenesis disorders (PBDs) in humans. This spectrum of autosomal recessive metabolic disorders is characterized by defective peroxisome assembly and impaired peroxisomal functions. PBDs are caused by mutations in the peroxisomal biogenesis factors, which are required for the correct compartmentalization of peroxisomal matrix enzymes. Recent work from patient cells that contain the Pex1(G843D) point mutant suggested that the inhibition of the lysosome, and therefore the block of pexophagy, was beneficial for peroxisomal function. The resulting working model proposed that Pex1 may not be essential for matrix protein import at all, but rather for the prevention of pexophagy. Thus, the observed matrix protein import defect would not be caused by a lack of Pex1 activity, but rather by enhanced removal of peroxisomal membranes via pexophagy. In the present study, we can show that the specific block of PEX1 deletion-induced pexophagy does not restore peroxisomal matrix protein import or the peroxisomal function in beta-oxidation in yeast. Therefore, we conclude that Pex1 is directly and essentially involved in peroxisomal matrix protein import, and that the PEX1 deletion-induced pexophagy is not responsible for the defect in peroxisomal function. In order to point out the conserved mechanism, we discuss our findings in the context of the working models of peroxisomal biogenesis and pexophagy in yeasts and mammals.

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“…The need for ATP comes only at the next steps, when the machinery is reset, that is, when the receptor is extracted back into the cytosol thus freeing the DTM for another protein import event [55]. This involves (a) monoubiquitination of PEX5 at a conserved cysteine residue located near the N terminus of the protein by the RING peroxins of the DTM [56][57][58], (b) extraction of monoubiquitinated PEX5 into the cytosol by the ATP-dependent mechanoenzymes PEX1 and PEX6, a step that also releases PEX7 from the DTM [51,55,[59][60][61], and, finally, (c) the rapid deubiquitination of Ub-PEX5 in the cytosol [62][63][64].…”

Section: Introductionmentioning

confidence: 99%

The intrinsically disordered nature of the peroxisomal protein translocation machinery

et al. 2018

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Despite having a membrane that is impermeable to all but the smallest of metabolites, peroxisomes acquire their newly synthesized (cytosolic) matrix proteins in an already folded conformation. In some cases, even oligomeric proteins have been reported to translocate the organelle membrane. The protein sorting machinery that accomplishes this feat must be rather flexible and, unsurprisingly, several of its key components have large intrinsically disordered domains. Here, we provide an overview on these domains and their interactions trying to infer their functional roles in this protein sorting pathway.

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Role of PEX5 ubiquitination in maintaining peroxisome dynamics and homeostasis

Cited by 47 publications

References 111 publications

TRIM37 deficiency induces autophagy through deregulating the MTORC1-TFEB axis

TRIM37 deficiency induces autophagy through deregulating the MTORC1-TFEB axis

The Peroxisomal PTS1-Import Defect of PEX1- Deficient Cells Is Independent of Pexophagy in Saccharomyces cerevisiae

The intrinsically disordered nature of the peroxisomal protein translocation machinery

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