The membrane remodeling protein Pex11p activates the GTPase Dnm1p during peroxisomal fission

Williams, Chris; Opaliński, Łukasz; Landgraf, Christiane; Costello, Joseph L.; Schrader, Michael; Krikken, Arjen M; Knoops, Kèvin; Kram, Anita M.; Volkmer, Rudolf; Klei, Ida J. van der

doi:10.1073/pnas.1418736112

Cited by 70 publications

(60 citation statements)

References 41 publications

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“…Expression of PEX11β‐EGFP in PEX5 deficient cells promoted peroxisome elongation and subsequent division (Figure 5A) confirming earlier reports that PEX11β‐induced peroxisome proliferation is independent of peroxisomal metabolism 45, 54. As PEX11β also activates the fission GTPase Drp1,15 it likely increases the division rate β as well as the elongation speed v and lipid flow rate.…”

Section: Resultssupporting

confidence: 87%

A role for Mitochondrial Rho GTPase 1 (MIRO1) in motility and membrane dynamics of peroxisomes

Castro

Richards

Metz

et al. 2018

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Peroxisomes are dynamic organelles which fulfil essential roles in lipid and ROS metabolism. Peroxisome movement and positioning allows interaction with other organelles and is crucial for their cellular function. In mammalian cells, such movement is microtubule‐dependent and mediated by kinesin and dynein motors. The mechanisms of motor recruitment to peroxisomes are largely unknown, as well as the role this plays in peroxisome membrane dynamics and proliferation. Here, using a combination of microscopy, live‐cell imaging analysis and mathematical modelling, we identify a role for Mitochondrial Rho GTPase 1 (MIRO1) as an adaptor for microtubule‐dependent peroxisome motility in mammalian cells. We show that MIRO1 is targeted to peroxisomes and alters their distribution and motility. Using a peroxisome‐targeted MIRO1 fusion protein, we demonstrate that MIRO1‐mediated pulling forces contribute to peroxisome membrane elongation and proliferation in cellular models of peroxisome disease. Our findings reveal a molecular mechanism for establishing peroxisome‐motor protein associations in mammalian cells and provide new insights into peroxisome membrane dynamics in health and disease.

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Section: Resultssupporting

confidence: 87%

A role for Mitochondrial Rho GTPase 1 (MIRO1) in motility and membrane dynamics of peroxisomes

Castro

Richards

Metz

et al. 2018

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“…Because DRP1 in mammalian cells is recruited to PEX11‐enriched peroxisomal membranes , evidence was sought for a functional link and/or a physical interaction between H. polymorpha Dnm11 and Pex11. Direct interaction was confirmed by co‐precipitation from wild‐type (WT) H. polymorpha cell lysates and interactions between Dnm1 expressed and purified from Escherichia coli and purified yeast Pex11 . Similar interactions were also reported between PEX11β and DRP1 in mammalian cells .…”

Section: Introductionsupporting

confidence: 67%

Peroxisome biogenesis, membrane contact sites, and quality control

et al. 2018

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Peroxisomes are conserved organelles of eukaryotic cells with important roles in cellular metabolism, human health, redox homeostasis, as well as intracellular metabolite transfer and signaling. We review here the current status of the different co‐existing modes of biogenesis of peroxisomal membrane proteins demonstrating the fascinating adaptability in their targeting and sorting pathways. While earlier studies focused on peroxisomes as autonomous organelles, the necessity of the ER and potentially even mitochondria as sources of peroxisomal membrane proteins and lipids has come to light in recent years. Additionally, the intimate physical juxtaposition of peroxisomes with other organelles has transitioned from being viewed as random encounters to a growing appreciation of the expanding roles of such inter‐organellar membrane contact sites in metabolic and regulatory functions. Peroxisomal quality control mechanisms have also come of age with a variety of mechanisms operating both during biogenesis and in the cellular response to environmental cues.

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“…After targeting, DLP1 self-assembles into large ring-like structures. (c) Pex11β acts as a GTPase activating protein on DLP1 [183]. GTP hydrolysis by DLP1 leads to constriction of the DLP1 ring and results in final membrane scission.…”

Section: Kinases and Phosphatases In Peroxisome Biogenesis And Metabomentioning

confidence: 99%

“…2). A new and crucial function of yeast Pex11p and Pex11β in the final step of peroxisomal fission was very recently identified [183]. H. polymorpha Pex11p was shown to be necessary for the function of the dynamin-like GTPase HpDnm1p (DLP1) in vivo and to physically interact with Dnm1p via conserved amino acid stretches in the N-terminal domain.…”

Section: The Pex11p Family -Membrane Deformation and Morementioning

confidence: 99%

Proliferation and fission of peroxisomes — An update

Schrader

Costello

Godinho

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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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.

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The membrane remodeling protein Pex11p activates the GTPase Dnm1p during peroxisomal fission

Cited by 70 publications

References 41 publications

A role for Mitochondrial Rho GTPase 1 (MIRO1) in motility and membrane dynamics of peroxisomes

A role for Mitochondrial Rho GTPase 1 (MIRO1) in motility and membrane dynamics of peroxisomes

Peroxisome biogenesis, membrane contact sites, and quality control

Proliferation and fission of peroxisomes — An update

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