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Plant Physiology Jan 2018Environmental stress activates autophagy and leads to autophagosome formation at the endoplasmic reticulum. (Review)
Review
Environmental stress activates autophagy and leads to autophagosome formation at the endoplasmic reticulum.
Topics: Autophagosomes; Autophagy; Cell Membrane; Models, Biological
PubMed: 29061903
DOI: 10.1104/pp.17.01236 -
Journal of Molecular Biology May 2016Macroautophagy is an evolutionarily conserved dynamic pathway that functions primarily in a degradative manner. A basal level of macroautophagy occurs constitutively,... (Review)
Review
Macroautophagy is an evolutionarily conserved dynamic pathway that functions primarily in a degradative manner. A basal level of macroautophagy occurs constitutively, but this process can be further induced in response to various types of stress including starvation, hypoxia and hormonal stimuli. The general principle behind macroautophagy is that cytoplasmic contents can be sequestered within a transient double-membrane organelle, an autophagosome, which subsequently fuses with a lysosome or vacuole (in mammals, or yeast and plants, respectively), allowing for degradation of the cargo followed by recycling of the resulting macromolecules. Through this basic mechanism, macroautophagy has a critical role in cellular homeostasis; however, either insufficient or excessive macroautophagy can seriously compromise cell physiology, and thus, it needs to be properly regulated. In fact, a wide range of diseases are associated with dysregulation of macroautophagy. There has been substantial progress in understanding the regulation and molecular mechanisms of macroautophagy in different organisms; however, many questions concerning some of the most fundamental aspects of macroautophagy remain unresolved. In this review, we summarize current knowledge about macroautophagy mainly in yeast, including the mechanism of autophagosome biogenesis, the function of the core macroautophagic machinery, the regulation of macroautophagy and the process of cargo recognition in selective macroautophagy, with the goal of providing insights into some of the key unanswered questions in this field.
Topics: Autophagosomes; Autophagy; Organelle Biogenesis; Saccharomyces cerevisiae
PubMed: 26908221
DOI: 10.1016/j.jmb.2016.02.021 -
Acta Biochimica Et Biophysica Sinica Aug 2023Autophagy, an efficient and effective approach to clear rapidly damaged organelles, macromolecules, and other harmful cellular components, enables the recycling of...
Autophagy, an efficient and effective approach to clear rapidly damaged organelles, macromolecules, and other harmful cellular components, enables the recycling of nutrient materials and supply of nutrients to maintain cellular homeostasis. Ubiquitination plays an important regulatory role in autophagy. This paper summarizes the most recent progress in ubiquitin modification in various stages of autophagy, including initiation, elongation, and termination. Moreover, this paper shows that ubiquitination is an important way through which selective autophagy achieves substrate specificity. Furthermore, we note the distinction between monoubiquitination and polyubiquitination in the regulation of autophagy. Compared with monoubiquitination, polyubiquitination is a more common strategy to regulate the activity of the autophagy molecular machinery. In addition, the role of ubiquitination in the closure and fusion of autophagosomes warrants further study. This article not only clarifies the regulatory mechanism of autophagy but also contributes to a deeper understanding of the importance of ubiquitination modification.
Topics: Autophagy; Ubiquitination; Autophagosomes; Ubiquitin; Cognition
PubMed: 37587758
DOI: 10.3724/abbs.2023149 -
Autophagy Jun 2022STX17 (syntaxin 17) mediates autophagosome-lysosome fusion, and the translocation of STX17 to autophagosomes is characteristic of this process. STX17 arrives at...
STX17 (syntaxin 17) mediates autophagosome-lysosome fusion, and the translocation of STX17 to autophagosomes is characteristic of this process. STX17 arrives at autophagosomes when they are closed, stays there for approximately 10 min to promote fusion with lysosomes, and leaves when the autolysosomes are mature. However, the mechanism of this transient visit remains largely unknown. Here, we summarize the current knowledge about this phenomenon, including a recently discovered retrieval mechanism, and discuss remaining questions. MAM: mitochondria-associated membrane; SNX: sorting nexin; STX17: syntaxin 17.
Topics: Autophagosomes; Autophagy; Lysosomes; Membrane Fusion; Qa-SNARE Proteins
PubMed: 35613317
DOI: 10.1080/15548627.2022.2079337 -
Journal of Molecular Biology Jan 2020Eukaryotic cells have the capacity to degrade intracellular components through a lysosomal degradation pathway called macroautophagy (henceforth referred to as... (Review)
Review
Eukaryotic cells have the capacity to degrade intracellular components through a lysosomal degradation pathway called macroautophagy (henceforth referred to as autophagy) in which superfluous or damaged cytosolic entities are engulfed and separated from the rest of the cell constituents into double membraned vesicles known as autophagosomes. Autophagosomes then fuse with endosomes and lysosomes, where cargo is broken down into basic building blocks that are released to the cytoplasm for the cell to reuse. Autophagic degradation can target either cytoplasmic material in bulk (non-selective autophagy) or particular cargo in what is called selective autophagy. Proper autophagic turnover requires the orchestrated participation of several players that need to be tightly and temporally coordinated. Whereas a large number of autophagy-related (ATG) proteins have been identified and their functions and regulation are starting to be understood, there is substantially less knowledge regarding the specific lipids constituting the autophagic membranes as well as their role in initiating, enabling or regulating the autophagic process. This review focuses on lipids and their corresponding binding proteins that are crucial in the process of selective autophagy.
Topics: Animals; Autophagosomes; Autophagy; Autophagy-Related Proteins; Humans; Lipid Metabolism; Macroautophagy; Mitophagy; Protein Binding
PubMed: 31202884
DOI: 10.1016/j.jmb.2019.05.051 -
Molecules and Cells Jan 2018Atg5 and Atg7 have long been considered as essential molecules for autophagy. However, we found that cells lacking these molecules still form autophagic vacuoles and... (Review)
Review
Atg5 and Atg7 have long been considered as essential molecules for autophagy. However, we found that cells lacking these molecules still form autophagic vacuoles and perform autophagic protein degradation when subjected to certain stressors. During this unconventional autophagy pathway, autophagosomes appeared to be generated in a Rab9-dependent manner by the fusion of vesicles derived from the -Golgi and late endosomes. Therefore, mammalian autophagy can occur via at least two different pathways; the Atg5/Atg7-dependent conventional pathway and an Atg5/Atg7-independent alternative pathway.
Topics: Animals; Autophagosomes; Autophagy; Autophagy-Related Protein 5; Autophagy-Related Protein 7; Humans; Lysosomes; Microtubule-Associated Proteins; Models, Biological; Phagosomes
PubMed: 29370693
DOI: 10.14348/molcells.2018.2215 -
Molecular Cell Apr 2022As one of the two highly conserved cellular degradation systems, autophagy plays a critical role in regulation of protein, lipid, and organelle quality control and... (Review)
Review
As one of the two highly conserved cellular degradation systems, autophagy plays a critical role in regulation of protein, lipid, and organelle quality control and cellular homeostasis. This evolutionarily conserved pathway singles out intracellular substrates for elimination via encapsulation within a double-membrane vesicle and delivery to the lysosome for degradation. Multiple cancers disrupt normal regulation of autophagy and hijack its degradative ability to remodel their proteome, reprogram their metabolism, and adapt to environmental challenges, making the autophagy-lysosome system a prime target for anti-cancer interventions. Here, we discuss the roles of autophagy in tumor progression, including cancer-specific mechanisms of autophagy regulation and the contribution of tumor and host autophagy in metabolic regulation, immune evasion, and malignancy. We further discuss emerging proteomics-based approaches for systematic profiling of autophagosome-lysosome composition and contents. Together, these approaches are uncovering new features and functions of autophagy, leading to more effective strategies for targeting this pathway in cancer.
Topics: Autophagosomes; Autophagy; Humans; Lysosomes; Neoplasms; Quality Control
PubMed: 35452618
DOI: 10.1016/j.molcel.2022.03.023 -
Autophagy Jul 2023Autophagosome isolation enables the thorough investigation of structural components and engulfed materials. Recently, we introduced a novel antibody-based FACS-mediated...
Autophagosome isolation enables the thorough investigation of structural components and engulfed materials. Recently, we introduced a novel antibody-based FACS-mediated method for isolation of native macroautophagic/autophagic vesicles and confirmed the quality of the preparations. We performed phospholipidomic and proteomic analyses to characterize autophagic vesicle-associated phospholipids and protein cargoes under different autophagy conditions. Lipidomic analyses identified phosphoglycerides and sphingomyelins within autophagic vesicles and revealed that the lipid composition was unaffected by different rates of autophagosome formation. Proteomic analyses identified more than 4500 potential autophagy substrates and showed that in comparison to autophagic vesicles isolated under basal autophagy conditions, starvation only marginally affected the cargo profile. Proteasome inhibition, however, resulted in the enhanced degradation of ubiquitin-proteasome system components. Taken together, the novel isolation method enriched large quantities of autophagic vesicles and enabled detailed analyses of their lipid and cargo composition.
Topics: Autophagy; Proteasome Endopeptidase Complex; Proteomics; Autophagosomes; Lipids
PubMed: 36416088
DOI: 10.1080/15548627.2022.2151188 -
Autophagy Aug 2020A key feature of macroautophagy (hereafter autophagy) is the formation of the phagophore, a double-membrane compartment sequestering cargos and finally maturing into a...
A key feature of macroautophagy (hereafter autophagy) is the formation of the phagophore, a double-membrane compartment sequestering cargos and finally maturing into a vesicle termed an autophagosome; however, where these membranes originate from is not clear. In a previous study, researchers from the Rubinsztein lab proposed a model in which the autophagosome can evolve from the RAB11A-positive recycling endosome. In their recent paper, they determine that DNM2 (dynamin 2) functions in scission of the recycling endosome, and the release of the autophagosome precursor. These findings explain how the centronuclear myopathy (CNM) mutation in DNM2 results in the accumulation of immature autophagic structures.
Topics: Animals; Autophagosomes; Autophagy; Autophagy-Related Proteins; Cell Membrane; Dynamin II; Endosomes; Humans; Mice; Mutation; Phenotype
PubMed: 32544363
DOI: 10.1080/15548627.2020.1779468 -
The FEBS Journal May 2017Phosphatidylinositol-3-phosphate (PI3P) is a key player in membrane dynamics and trafficking regulation. Most PI3P is associated with endosomal membranes and with the... (Review)
Review
Phosphatidylinositol-3-phosphate (PI3P) is a key player in membrane dynamics and trafficking regulation. Most PI3P is associated with endosomal membranes and with the autophagosome preassembly machinery, presumably at the endoplasmic reticulum. The enzyme responsible for most PI3P synthesis, VPS34 and proteins such as Beclin1 and ATG14L that regulate PI3P levels are positive modulators of autophagy initiation. It had been assumed that a local PI3P pool was present at autophagosomes and preautophagosomal structures, such as the omegasome and the phagophore. This was recently confirmed by the demonstration that PI3P-binding proteins participate in the complex sequence of signalling that results in autophagosome assembly and activity. Here we summarize the historical discoveries of PI3P lipid kinase involvement in autophagy, and we discuss the proposed role of PI3P during autophagy, notably during the autophagosome biogenesis sequence.
Topics: Adaptor Proteins, Vesicular Transport; Animals; Autophagosomes; Autophagy; Autophagy-Related Proteins; Beclin-1; Class II Phosphatidylinositol 3-Kinases; Class III Phosphatidylinositol 3-Kinases; Endoplasmic Reticulum; Endosomes; Humans; Lysosomes; Membrane Microdomains; Models, Biological; Organelle Biogenesis; Phosphatidylinositol Phosphates; Second Messenger Systems
PubMed: 27973739
DOI: 10.1111/febs.13987