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Cell Research Feb 2022Under stress, the endomembrane system undergoes reorganization to support autophagosome biogenesis, which is a central step in autophagy. How the endomembrane system...
Under stress, the endomembrane system undergoes reorganization to support autophagosome biogenesis, which is a central step in autophagy. How the endomembrane system remodels has been poorly understood. Here we identify a new type of membrane contact formed between the ER-Golgi intermediate compartment (ERGIC) and the ER-exit site (ERES) in the ER-Golgi system, which is essential for promoting autophagosome biogenesis induced by different stress stimuli. The ERGIC-ERES contact is established by the interaction between TMED9 and SEC12 which generates a short distance opposition (as close as 2-5 nm) between the two compartments. The tight membrane contact allows the ERES-located SEC12 to transactivate COPII assembly on the ERGIC. In addition, a portion of SEC12 also relocates to the ERGIC. Through both mechanisms, the ERGIC-ERES contact promotes formation of the ERGIC-derived COPII vesicle, a membrane precursor of the autophagosome. The ERGIC-ERES contact is physically and functionally different from the TFG-mediated ERGIC-ERES adjunction involved in secretory protein transport, and therefore defines a unique endomembrane structure generated upon stress conditions for autophagic membrane formation.
Topics: Autophagosomes; Autophagy; Endoplasmic Reticulum; Golgi Apparatus; Protein Transport
PubMed: 34561617
DOI: 10.1038/s41422-021-00563-0 -
Autophagy Nov 2021It would be quite convenient if every protein had one distinct function, one distinct role in just a single cellular process. In the field of macroautophagy/autophagy,...
It would be quite convenient if every protein had one distinct function, one distinct role in just a single cellular process. In the field of macroautophagy/autophagy, however, we are increasingly finding that this is not the case; several autophagy proteins have two or more roles within the process of autophagy and many even "moonlight" as functional members of entirely different cellular processes. This is perhaps best exemplified by the Atg8-family proteins. These dynamic proteins have already been reported to serve several functions both within autophagy (membrane tethering, membrane fusion, binding to cargo receptors, binding to autophagy machinery) and beyond (LC3-associated phagocytosis, formation of EDEMosomes, immune signaling) but as Maruyama and colleagues suggest in their recent report, this list of functions may not yet be complete.
Topics: Animals; Autophagosomes; Autophagy; Autophagy-Related Protein 8 Family; Binding Sites; Humans; Models, Molecular; Molecular Docking Simulation; Mutation
PubMed: 34482799
DOI: 10.1080/15548627.2021.1967566 -
Advanced Science (Weinheim,... Sep 2023Ferroptosis plays an essential role in the development of diabetes and its complications, suggesting potential therapeutic strategies targeting ferroptosis. Secretory...
Ferroptosis plays an essential role in the development of diabetes and its complications, suggesting potential therapeutic strategies targeting ferroptosis. Secretory autophagosomes (SAPs) carrying cytoplasmic cargoes have been recognized as novel nano-warrior to defeat diseases. Here, it is hypothesized that SAPs derived from human umbilical vein endothelial cells (HUVECs) can restore the function of skin repair cells by inhibiting ferroptosis to promote diabetic wound healing. High glucose (HG)-caused ferroptosis in human dermal fibroblasts (HDFs) is observed in vitro, which results in impaired cellular function. SAPs successfully inhibit ferroptosis in HG-HDFs, thereby improving their proliferation and migration. Further research show that the inhibitory effect of SAPs on ferroptosis resulted from a decrease in endoplasmic reticulum (ER) stress-regulated generation of free ferrous ions (Fe ) in HG-HDFs and an increase in exosome release to discharge free Fe from HG-HDFs. Additionally, SAPs promote the proliferation, migration, and tube formation of HG-HUVECs. Then the SAPs are loaded into gelatin-methacryloyl (GelMA) hydrogels to fabricate functional wound dressings. The results demonstrate the therapeutic effect of Gel-SAPs on diabetic wounds by restoring the normal behavior of skin repair cells. These findings suggest a promising SAP-based strategy for the treatment of ferroptosis-associated diseases.
Topics: Humans; Autophagosomes; Ferroptosis; Wound Healing; Diabetes Mellitus; Human Umbilical Vein Endothelial Cells
PubMed: 37387572
DOI: 10.1002/advs.202300414 -
Journal of Molecular Histology Feb 2021Apoptosis and clearance of dead cells is highly evolutionarily conserved from nematode to humans, which is crucial to the growth and development of multicellular... (Review)
Review
Apoptosis and clearance of dead cells is highly evolutionarily conserved from nematode to humans, which is crucial to the growth and development of multicellular organism. Fail to remove apoptotic cells often lead to homeostasis imbalance, fatal autoimmune diseases, and neurodegenerative diseases. Small ubiquitin-related modifiers (SUMOs) modification is a post-translational modification of ubiquitin proteins mediated by the sentrin-specific proteases (SENPs) family. SUMO modification is widely involved in many cellular biological process, and abnormal SUMO modification is also closely related to many major human diseases. Recent researches have revealed that SUMO modification event occurs during apoptosis and clearance of apoptotic cells, and plays an important role in the regulation of apoptotic signaling pathways. This review summarizes some recent progress in the revelation of regulatory mechanisms of these pathways and provides some potential researching hotpots of the SUMO modification regulation to apoptosis.
Topics: Apoptosis; Humans; Mitochondria; Phagosomes; Protein Processing, Post-Translational; Signal Transduction; Small Ubiquitin-Related Modifier Proteins
PubMed: 33225418
DOI: 10.1007/s10735-020-09924-2 -
Frontiers in Immunology 2020Phagocytosis is an ancient, highly conserved process in all multicellular organisms, through which the host can protect itself against invading microorganisms and... (Review)
Review
Phagocytosis is an ancient, highly conserved process in all multicellular organisms, through which the host can protect itself against invading microorganisms and environmental particles, as well as remove self-apoptotic cells/cell debris to maintain tissue homeostasis. In crustacean, phagocytosis by hemocyte has also been well-recognized as a crucial defense mechanism for the host against infectious agents such as bacteria and viruses. In this review, we summarized the current knowledge of hemocyte-mediated phagocytosis, in particular focusing on the related receptors for recognition and internalization of pathogens as well as the downstream signal pathways and intracellular regulators involved in the process of hemocyte phagocytosis. We attempted to gain a deeper understanding of the phagocytic mechanism of different hemocytes and their contribution to the host defense immunity in crustaceans.
Topics: Animals; Cell Adhesion Molecules; Crustacea; Hemocytes; Host-Pathogen Interactions; Immunity, Innate; Lectins; Opsonin Proteins; Phagocytes; Phagocytosis; Phagosomes; Pore Forming Cytotoxic Proteins; Receptors, Pattern Recognition; Receptors, Scavenger; Signal Transduction
PubMed: 32194551
DOI: 10.3389/fimmu.2020.00268 -
Journal of Experimental Botany May 2020Autophagy is a universal mechanism that facilitates the degradation of unwanted cytoplasmic components in eukaryotic cells. In this review, we highlight recent... (Review)
Review
Autophagy is a universal mechanism that facilitates the degradation of unwanted cytoplasmic components in eukaryotic cells. In this review, we highlight recent developments in the investigation of the role of autophagy in lipid homeostasis in plants by comparison with algae, yeast, and animals. We consider the storage compartments that form the sources of lipids in plants, and the roles that autophagy plays in the synthesis of triacylglycerols and in the formation and maintenance of lipid droplets. We also consider the relationship between lipids and the biogenesis of autophagosomes, and the role of autophagy in the degradation of lipids in plants.
Topics: Animals; Autophagosomes; Autophagy; Lipid Droplets; Lipids; Plants
PubMed: 32080724
DOI: 10.1093/jxb/eraa082 -
Frontiers in Immunology 2021Following phagocytosis, the nascent phagosome undergoes maturation to become a phagolysosome with an acidic, hydrolytic, and often oxidative lumen that can efficiently... (Review)
Review
Following phagocytosis, the nascent phagosome undergoes maturation to become a phagolysosome with an acidic, hydrolytic, and often oxidative lumen that can efficiently kill and digest engulfed microbes, cells, and debris. The fusion of phagosomes with lysosomes is a principal driver of phagosomal maturation and is targeted by several adapted intracellular pathogens. Impairment of this process has significant consequences for microbial infection, tissue inflammation, the onset of adaptive immunity, and disease. Given the importance of phagosome-lysosome fusion to phagocyte function and the many virulence factors that target it, it is unsurprising that multiple molecular pathways have evolved to mediate this essential process. While the full range of these pathways has yet to be fully characterized, several pathways involving proteins such as members of the Rab GTPases, tethering factors and SNAREs have been identified. Here, we summarize the current state of knowledge to clarify the ambiguities in the field and construct a more comprehensive phagolysosome formation model. Lastly, we discuss how other cellular pathways help support phagolysosome biogenesis and, consequently, phagocyte function.
Topics: Animals; Autophagy; Humans; Lysosomes; Membrane Fusion; Phagocytes; Phagocytosis; Phagosomes; SNARE Proteins; rab GTP-Binding Proteins
PubMed: 33717183
DOI: 10.3389/fimmu.2021.636078 -
Developmental Cell Dec 2023The sequence of morphological intermediates that leads to mammalian autophagosome formation and closure is a crucial yet poorly understood issue. Previous studies have...
The sequence of morphological intermediates that leads to mammalian autophagosome formation and closure is a crucial yet poorly understood issue. Previous studies have shown that yeast autophagosomes evolve from cup-shaped phagophores with only one closure point, and mammalian studies have inferred that mammalian phagophores also have single openings. Our superresolution microscopy studies in different human cell lines in conditions of basal and nutrient-deprivation-induced autophagy identified autophagosome precursors with multifocal origins that evolved into unexpected finger-like phagophores with multiple openings before becoming more spherical structures. Compatible phagophore structures were observed with whole-mount and conventional electron microscopy. This sequence of events was visualized using advanced SIM superresolution live microscopy. The finger-shaped phagophore apertures remained open when ESCRT function was compromised. The efficient closure of autophagic structures is important for their release from the recycling endosome. This has important implications for understanding how autophagosomes form and capture various cargoes.
Topics: Animals; Humans; Autophagosomes; Autophagy; Endosomes; Cell Line; Phagocytosis; Mammals
PubMed: 37683632
DOI: 10.1016/j.devcel.2023.08.016 -
ELife Jun 2024A change in the electric charge of autophagosome membranes controls the recruitment of SNARE proteins to ensure that membrane fusion occurs at the right time during...
A change in the electric charge of autophagosome membranes controls the recruitment of SNARE proteins to ensure that membrane fusion occurs at the right time during autophagy.
Topics: Autophagy; Autophagosomes; Membrane Fusion; SNARE Proteins; Humans; Animals
PubMed: 38831693
DOI: 10.7554/eLife.99181 -
The Journal of Cell Biology Aug 2020Liquid-liquid phase separation (LLPS) compartmentalizes and concentrates biomacromolecules into distinct condensates. Liquid-like condensates can transition into gel and... (Review)
Review
Liquid-liquid phase separation (LLPS) compartmentalizes and concentrates biomacromolecules into distinct condensates. Liquid-like condensates can transition into gel and solid states, which are essential for fulfilling their different functions. LLPS plays important roles in multiple steps of autophagy, mediating the assembly of autophagosome formation sites, acting as an unconventional modulator of TORC1-mediated autophagy regulation, and triaging protein cargos for degradation. Gel-like, but not solid, protein condensates can trigger formation of surrounding autophagosomal membranes. Stress and pathological conditions cause aberrant phase separation and transition of condensates, which can evade surveillance by the autophagy machinery. Understanding the mechanisms underlying phase separation and transition will provide potential therapeutic targets for protein aggregation diseases.
Topics: Animals; Autophagosomes; Autophagy-Related Proteins; Humans; Macroautophagy; Mechanistic Target of Rapamycin Complex 1; Phase Transition; Protein Aggregates; Protein Aggregation, Pathological; Protein Transport; Proteolysis; Signal Transduction
PubMed: 32603410
DOI: 10.1083/jcb.202004062