Nucleophagy-Implications for Microautophagy and Health.
Florian B. Otto,Michael Thumm +1 more
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TLDR
Nucleophagy, the selective subtype of autophagy that targets nuclear material for autophagic degradation, was not only shown to be a model system for the study of selective macroautophagosome biogenesis, but also for elucidating the role of the core Autophagic machinery within microautophagy.Abstract:
Nucleophagy, the selective subtype of autophagy that targets nuclear material for autophagic degradation, was not only shown to be a model system for the study of selective macroautophagy, but also for elucidating the role of the core autophagic machinery within microautophagy Nucleophagy also emerged as a system associated with a variety of disease conditions including cancer, neurodegeneration and ageing Nucleophagic processes are part of natural cell development, but also act as a response to various stress conditions Upon releasing small portions of nuclear material, micronuclei, the autophagic machinery transfers these micronuclei to the vacuole for subsequent degradation Despite sharing many cargos and requiring the core autophagic machinery, recent investigations revealed the aspects that set macro- and micronucleophagy apart Central to the discrepancies found between macro- and micronucleophagy is the nucleus vacuole junction, a large membrane contact site formed between nucleus and vacuole Exclusion of nuclear pore complexes from the junction and its exclusive degradation by micronucleophagy reveal compositional differences in cargo Regarding their shared reliance on the core autophagic machinery, micronucleophagy does not involve normal autophagosome biogenesis observed for macronucleophagy, but instead maintains a unique role in overall microautophagy, with the autophagic machinery accumulating at the neck of budding vesiclesread more
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Challenges and Therapeutic Opportunities of Autophagy in Cancer Therapy.
TL;DR: This study discussed the results of several studies that evaluated autophagy as a therapeutic strategy in cancer, both through the modulation of therapeutic resistance and the death of cancer cells, and the role of Autophagy in the biology of cancer stem cells.
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Autophagy Modulators in Cancer Therapy.
TL;DR: In this article, a review summarizes the most recent research into understanding the different types and mechanisms of autophagy, with particular emphasis on those that are undergoing clinical and preclinical cancer research.
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Autophagy-Mediated Clearance of Free Genomic DNA in the Cytoplasm Protects the Growth and Survival of Cancer Cells.
Mengfei Yao,Yaqian Wu,Yanan Cao,Haijing Liu,Ningning Ma,Yijie Chai,Shuang Zhang,Hong Zhang,Lin Nong,Li Liang,Bo Zhang +10 more
TL;DR: The investigation revealed DNA autophagy in breast cancer cells with high MN formation and autophagic inhibition could be a potential therapeutic approach for cancer Cells with high DNA autophile activity.
Book ChapterDOI
Assessment of mammalian endosomal microautophagy.
TL;DR: In this paper, the authors used biochemical and imaging-based methods to track eMI activity in vitro with isolated LE/MVBs and in cells in culture using fluorescent reporters and highlight approaches to distinguish whether a protein is a substrate of eMI or CMA.
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Locked in a vicious cycle: the connection between genomic instability and a loss of protein homeostasis
Wouter Huiting,Steven Bergink +1 more
TL;DR: In certain cases, such as aneuploidy, a loss of protein homeostasis appears to be a crucial mechanism for pathology, which indicates that enhancing protein quality control systems could be a promising therapeutic strategy in diseases associated with genomic instability.
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Journal ArticleDOI
Endosome-Associated Complex, ESCRT-II, Recruits Transport Machinery for Protein Sorting at the Multivesicular Body
TL;DR: This study characterizes ESCRT-II, a soluble approximately 155 kDa protein complex formed by the class E Vps proteins Vps22, Vps25, and Vps36, and proposes that the ESCRT complexes perform a coordinated cascade of events to select and sort MVB cargoes for delivery to the lumen of the vacuole/lysosome.
Journal ArticleDOI
Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease
Maria Filimonenko,Susanne Stuffers,Camilla Raiborg,Ai Yamamoto,Lene Malerød,Elizabeth M. C. Fisher,Adrian M. Isaacs,Andreas Brech,Harald Stenmark,Anne Simonsen +9 more
TL;DR: It is shown that autophagic degradation is inhibited in cells depleted of ESCRT subunits and in cells expressing CHMP2B mutants, leading to accumulation of protein aggregates containing ubiquitinated proteins, p62 and Alfy, and functional MVBs are required for clearance of TDP-43 and expanded polyglutamine aggregates associated with Huntington's disease.