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      Mechanisms of Selective Autophagy

      1 , 1
      Annual Review of Cell and Developmental Biology
      Annual Reviews

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          Abstract

          Selective autophagy is the lysosomal degradation of specific intracellular components sequestered into autophagosomes, late endosomes, or lysosomes through the activity of selective autophagy receptors (SARs). SARs interact with autophagy-related (ATG)8 family proteins via sequence motifs called LC3-interacting region (LIR) motifs in vertebrates and Atg8-interacting motifs (AIMs) in yeast and plants. SARs can be divided into two broad groups: soluble or membrane bound. Cargo or substrate selection may be independent or dependent of ubiquitin labeling of the cargo. In this review, we discuss mechanisms of mammalian selective autophagy with a focus on the unifying principles employed in substrate recognition, interaction with the forming autophagosome via LIR-ATG8 interactions, and the recruitment of core autophagy components for efficient autophagosome formation on the substrate.

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          Most cited references182

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          Biomolecular condensates: organizers of cellular biochemistry

          In addition to membrane-bound organelles, eukaryotic cells feature various membraneless compartments, including the centrosome, the nucleolus and various granules. Many of these compartments form through liquid–liquid phase separation, and the principles, mechanisms and regulation of their assembly as well as their cellular functions are now beginning to emerge.
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            The role of Atg proteins in autophagosome formation.

            Macroautophagy is mediated by a unique organelle, the autophagosome, which encloses a portion of cytoplasm for delivery to the lysosome. Autophagosome formation is dynamically regulated by starvation and other stresses and involves complicated membrane reorganization. Since the discovery of yeast Atg-related proteins, autophagosome formation has been dissected at the molecular level. In this review we describe the molecular mechanism of autophagosome formation with particular focus on the function of Atg proteins and the long-standing discussion regarding the origin of the autophagosome membrane.
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              Liquid phase condensation in cell physiology and disease.

              Phase transitions are ubiquitous in nonliving matter, and recent discoveries have shown that they also play a key role within living cells. Intracellular liquid-liquid phase separation is thought to drive the formation of condensed liquid-like droplets of protein, RNA, and other biomolecules, which form in the absence of a delimiting membrane. Recent studies have elucidated many aspects of the molecular interactions underlying the formation of these remarkable and ubiquitous droplets and the way in which such interactions dictate their material properties, composition, and phase behavior. Here, we review these exciting developments and highlight key remaining challenges, particularly the ability of liquid condensates to both facilitate and respond to biological function and how their metastability may underlie devastating protein aggregation diseases.
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                Author and article information

                Journal
                Annual Review of Cell and Developmental Biology
                Annu. Rev. Cell Dev. Biol.
                Annual Reviews
                1081-0706
                1530-8995
                October 06 2021
                October 06 2021
                : 37
                : 1
                : 143-169
                Affiliations
                [1 ]Molecular Cancer Research Group, Department of Medical Biology, University of Tromsø – The Arctic University of Norway, 9037 Tromsø, Norway;,
                Article
                10.1146/annurev-cellbio-120219-035530
                34152791
                d3757d80-0f82-44a6-ba0e-4c3cdb33fdfe
                © 2021
                History

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