Autophagy: A Forty-Year Search for a Missing Membrane Source

Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota, USA.
PLoS Biology (Impact Factor: 9.34). 03/2006; 4(2):e36. DOI: 10.1371/journal.pbio.0040036
Source: PubMed

ABSTRACT Autophagy is central to diverse biological processes in eukaryotes including animal development and cellular survival, and also to neurodegenerative diseases, but the origin of the membranes that make up autophagic vesicles is unknown.

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    • "During the induction of autophagy, the isolation membrane (phagophore) elongates and seals itself to produce an autophagosome3,12,46. The autophagosome fuses with endocytic cargos to generate a mature autophagosome. "
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    ABSTRACT: WASH (Wiskott-Aldrich syndrome protein (WASP) and SCAR homolog) was identified to function in endosomal sorting via Arp2/3 activation. We previously demonstrated that WASH is a new interactor of BECN1 and present in the BECN1-PIK3C3 complex with AMBRA1. The AMBRA1-DDB1-CUL4A complex is an E3 ligase for K63-linked ubiquitination of BECN1, which is required for starvation-induced autophagy. WASH suppresses autophagy by inhibition of BECN1 ubiquitination. However, how AMBRA1 is regulated during autophagy remains elusive. Here, we found that RNF2 associates with AMBRA1 to act as an E3 ligase to ubiquitinate AMBRA1 via K48 linkage. RNF2 mediates ubiquitination of AMBRA1 at lysine 45. Notably, RNF2 deficiency enhances autophagy induction. Upon autophagy induction, RNF2 potentiates AMBRA1 degradation with the help of WASH. WASH deficiency impairs the association of RNF2 with AMBRA1 to impede AMBRA1 degradation. Our findings reveal another novel layer of regulation of autophagy through WASH recruitment of RNF2 for AMBRA1 degradation leading to downregulation of autophagy.Cell Research advance online publication 1 July 2014; doi:10.1038/cr.2014.85.
    Cell Research 07/2014; 24(8). DOI:10.1038/cr.2014.85 · 12.41 Impact Factor
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    • "During the main pathway of autophagy, initially appearing membrane cisterns called phagophores capture portions of the cytoplasm in double-membrane autophagosomes. These vesicles then deliver cargo for lysosomal degradation [16,17]. Beclin 1, LC3II and p62 are considered to be the most important molecules during this process, and they are known as autophagy marker genes. "
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    ABSTRACT: Background Recent findings indicated that Derlin-1 has an important function in tumour progression. In this study, we aimed to determine whether Derlin-1 has an oncogene function as a cross-talk molecule with autophagy. Methods Cancer cells were treated with tunicamycin (TM) for 8 and 24 h. The expression of Derlin-1 and autophagy-related genes was determined by western blot. Autophagy was analysed by fluorescence microscopy after staining the cancer cells with monodansylcadaverine. The interaction between Derlin-1 and other proteins was identified using co-immunoprecipitation assay. Results Our study demonstrated high Derlin-1 expression levels in most non-small lung cancer cell lines. Derlin-1 expression was enhanced under endoplasmic reticulum (ER) stress. Previous studies revealed that TM triggers the initiation of autophagy by activating Beclin 1, converting LC3I to LC3II and degrading p62. Knockdown of Derlin-1 did not affect Beclin 1 and LC3II expression but disrupted the degradation of p62 under ER stress, which resulted in the blockage of autophagy flux. Furthermore, Derlin-1 and p62 were observed to interact under ER stress. Conclusion This study is the first report about the interaction between Derlin-1 and p62. Derlin-1 may function in tumour progression partially by interacting with p62.
    Cancer Cell International 06/2014; 14(1):50. DOI:10.1186/1475-2867-14-50 · 2.77 Impact Factor
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    • "The ends of the isolation membrane join together to form a double membranous vesicle. This new structure, known as an autophagosome, fuses with the lysosome forming the autolysosome , which is rich in hydrolases that act to enzymatically catabolize the vesicular contents (Juhasz and Neufeld, 2006). By isolating and then directing organelles and large biomolecules toward the lysosome, autophagy enables the cell to break down and redistribute molecules to pathways that are more critical for cell survival. "
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    ABSTRACT: Autophagy is important for a variety for virus life cycles. We sought to determine the role of autophagy in human BK polyomavirus (BKPyV) infection. The addition excess amino acids during viral infection reduced BKPyV infection. Perturbing autophagy levels using inhibitors, 3-MA, bafilomycin A1, and spautin-1, also reduced infection, while rapamycin treatment of host cells increased infection. siRNA knockdown of autophagy genes, ATG7 and Beclin-1, corresponded to a decrease in BKPyV infection. BKPyV infection not only correlated with autophagosome formation, but also virus particles localized to autophagy-specific compartments early in infection. These data support a novel role for autophagy in the promotion of BKPyV infection.
    Virology 05/2014; 456-457(1):87-95. DOI:10.1016/j.virol.2014.03.009 · 3.35 Impact Factor
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