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      ER as master regulator of membrane trafficking and organelle function

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          Abstract

          Wenzel et al. review how the endoplasmic reticulum controls the positioning, dynamics, and functions of other organelles via membrane contact sites.

          Abstract

          The endoplasmic reticulum (ER), which occupies a large portion of the cytoplasm, is the cell’s main site for the biosynthesis of lipids and carbohydrate conjugates, and it is essential for folding, assembly, and biosynthetic transport of secreted proteins and integral membrane proteins. The discovery of abundant membrane contact sites (MCSs) between the ER and other membrane compartments has revealed that, in addition to its biosynthetic and secretory functions, the ER plays key roles in the regulation of organelle dynamics and functions. In this review, we will discuss how the ER regulates endosomes, lysosomes, autophagosomes, mitochondria, peroxisomes, and the Golgi apparatus via MCSs. Such regulation occurs via lipid and Ca 2+ transfer and also via control of in trans dephosphorylation reactions and organelle motility, positioning, fusion, and fission. The diverse controls of other organelles via MCSs manifest the ER as master regulator of organelle biology.

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          Most cited references204

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          Autophagy: renovation of cells and tissues.

          Autophagy is the major intracellular degradation system by which cytoplasmic materials are delivered to and degraded in the lysosome. However, the purpose of autophagy is not the simple elimination of materials, but instead, autophagy serves as a dynamic recycling system that produces new building blocks and energy for cellular renovation and homeostasis. Here we provide a multidisciplinary review of our current understanding of autophagy's role in metabolic adaptation, intracellular quality control, and renovation during development and differentiation. We also explore how recent mouse models in combination with advances in human genetics are providing key insights into how the impairment or activation of autophagy contributes to pathogenesis of diverse diseases, from neurodegenerative diseases such as Parkinson disease to inflammatory disorders such as Crohn disease. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum

            Autophagy is the engulfment of cytosol and organelles by double-membrane vesicles termed autophagosomes. Autophagosome formation is known to require phosphatidylinositol 3-phosphate (PI(3)P) and occurs near the endoplasmic reticulum (ER), but the exact mechanisms are unknown. We show that double FYVE domain–containing protein 1, a PI(3)P-binding protein with unusual localization on ER and Golgi membranes, translocates in response to amino acid starvation to a punctate compartment partially colocalized with autophagosomal proteins. Translocation is dependent on Vps34 and beclin function. Other PI(3)P-binding probes targeted to the ER show the same starvation-induced translocation that is dependent on PI(3)P formation and recognition. Live imaging experiments show that this punctate compartment forms near Vps34-containing vesicles, is in dynamic equilibrium with the ER, and provides a membrane platform for accumulation of autophagosomal proteins, expansion of autophagosomal membranes, and emergence of fully formed autophagosomes. This PI(3)P-enriched compartment may be involved in autophagosome biogenesis. Its dynamic relationship with the ER is consistent with the idea that the ER may provide important components for autophagosome formation.
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              Rab GTPases as coordinators of vesicle traffic.

              Membrane trafficking between organelles by vesiculotubular carriers is fundamental to the existence of eukaryotic cells. Central in ensuring that cargoes are delivered to their correct destinations are the Rab GTPases, a large family of small GTPases that control membrane identity and vesicle budding, uncoating, motility and fusion through the recruitment of effector proteins, such as sorting adaptors, tethering factors, kinases, phosphatases and motors. Crosstalk between multiple Rab GTPases through shared effectors, or through effectors that recruit selective Rab activators, ensures the spatiotemporal regulation of vesicle traffic. Functional impairments of Rab pathways are associated with diseases, such as immunodeficiencies, cancer and neurological disorders.
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                Author and article information

                Journal
                J Cell Biol
                J Cell Biol
                jcb
                The Journal of Cell Biology
                Rockefeller University Press
                0021-9525
                1540-8140
                03 October 2022
                15 September 2022
                15 September 2022
                : 221
                : 10
                : e202205135
                Affiliations
                [1 ] Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, Oslo, Norway
                [2 ] Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
                Author notes
                Correspondence to Harald Stenmark: stenmark@ 123456ulrik.uio.no
                Author information
                https://orcid.org/0000-0002-5561-3344
                https://orcid.org/0000-0002-7246-7270
                https://orcid.org/0000-0002-1971-4252
                https://orcid.org/0000-0002-5406-5403
                Article
                jcb.202205135
                10.1083/jcb.202205135
                9481738
                36108241
                9761de0b-b831-4bd6-8e10-0b29cd2fe36e
                © 2022 Wenzel et al.

                This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).

                History
                : 30 May 2022
                : 16 August 2022
                : 22 August 2022
                Funding
                Funded by: Norwegian Cancer Society;
                Award ID: 198140
                Award ID: 182698
                Funded by: South-Eastern Norway Regional Health Authority;
                Award ID: 2018081
                Funded by: European Research Council, DOI http://dx.doi.org/10.13039/501100000781;
                Award ID: 788954
                Funded by: Radium Hospital Foundation;
                Funded by: Research Council of Norway;
                Award ID: 262652
                Categories
                Review
                Biochemistry
                Organelles
                Trafficking
                Metabolism

                Cell biology
                Cell biology

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