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Current Topics in Microbiology and... 2009Autophagy is a highly conserved cellular degradation process in which portions of cytosol and organelles are sequestered into a double-membrane vesicle, an... (Review)
Review
Autophagy is a highly conserved cellular degradation process in which portions of cytosol and organelles are sequestered into a double-membrane vesicle, an autophagosome, and delivered into a degradative organelle, the vacuole/lysosome, for breakdown and eventual recycling of the resulting macromolecules. This process relieves the cell from various stress conditions. Autophagy plays a critical role during cellular development and differentiation, functions in tumor suppression, and may be linked to life span extension. Autophagy also has diverse roles in innate and adaptive immunity, such as resistance to pathogen invasion. Substantial progress has been made in the identification of many autophagy-related (ATG) genes that are essential to drive this cellular process, including both selective and nonselective types of autophagy. Identification of the ATG genes in yeast, and the finding of orthologs in other organisms, reveals the conservation of the autophagic machinery in all eukaryotes. Here, we summarize our current knowledge about the machinery and molecular mechanism of autophagy.
Topics: Adaptive Immunity; Animals; Autophagy; Cytoplasmic Vesicles; Humans; Yeasts
PubMed: 19802558
DOI: 10.1007/978-3-642-00302-8_1 -
Cell Feb 2024Oocytes are among the longest-lived cells in the body and need to preserve their cytoplasm to support proper embryonic development. Protein aggregation is a major threat...
Oocytes are among the longest-lived cells in the body and need to preserve their cytoplasm to support proper embryonic development. Protein aggregation is a major threat for intracellular homeostasis in long-lived cells. How oocytes cope with protein aggregation during their extended life is unknown. Here, we find that mouse oocytes accumulate protein aggregates in specialized compartments that we named endolysosomal vesicular assemblies (ELVAs). Combining live-cell imaging, electron microscopy, and proteomics, we found that ELVAs are non-membrane-bound compartments composed of endolysosomes, autophagosomes, and proteasomes held together by a protein matrix formed by RUFY1. Functional assays revealed that in immature oocytes, ELVAs sequester aggregated proteins, including TDP-43, and degrade them upon oocyte maturation. Inhibiting degradative activity in ELVAs leads to the accumulation of protein aggregates in the embryo and is detrimental for embryo survival. Thus, ELVAs represent a strategy to safeguard protein homeostasis in long-lived cells.
Topics: Animals; Female; Mice; Autophagosomes; Cytoplasmic Vesicles; Lysosomes; Oocytes; Proteasome Endopeptidase Complex; Protein Aggregates; Proteolysis
PubMed: 38382525
DOI: 10.1016/j.cell.2024.01.031 -
Science (New York, N.Y.) Sep 2020Coronavirus genome replication is associated with virus-induced cytosolic double-membrane vesicles, which may provide a tailored microenvironment for viral RNA synthesis...
Coronavirus genome replication is associated with virus-induced cytosolic double-membrane vesicles, which may provide a tailored microenvironment for viral RNA synthesis in the infected cell. However, it is unclear how newly synthesized genomes and messenger RNAs can travel from these sealed replication compartments to the cytosol to ensure their translation and the assembly of progeny virions. In this study, we used cellular cryo-electron microscopy to visualize a molecular pore complex that spans both membranes of the double-membrane vesicle and would allow export of RNA to the cytosol. A hexameric assembly of a large viral transmembrane protein was found to form the core of the crown-shaped complex. This coronavirus-specific structure likely plays a key role in coronavirus replication and thus constitutes a potential drug target.
Topics: Animals; Cryoelectron Microscopy; Cytoplasmic Vesicles; Electron Microscope Tomography; Intracellular Membranes; Mice; Murine hepatitis virus; RNA, Viral; Viral Nonstructural Proteins; Virus Replication
PubMed: 32763915
DOI: 10.1126/science.abd3629 -
Photosynthesis Research Dec 2018Photosynthesis is a well-known process that has been intensively investigated, but less is known about the biogenesis of the thylakoid membrane that harbors the... (Review)
Review
Photosynthesis is a well-known process that has been intensively investigated, but less is known about the biogenesis of the thylakoid membrane that harbors the photosynthetic machinery. Thylakoid membranes are constituted by several components, the major ones being proteins and lipids. However, neither of these two are produced in the thylakoid membranes themselves but are targeted there by different mechanisms. The interior of the chloroplast, the stroma, is an aqueous compartment that prevents spontaneous transport of single lipids and/or membrane proteins due to their hydrophobicities. Thylakoid targeted proteins are encoded either in the nucleus or plastid, and thus some cross the envelope membrane before entering one of the identified thylakoid targeting pathways. However, the pathway for all thylakoid proteins is not known. Lipids are produced at the envelope membrane and have been proposed to reach the thylakoid membrane by different means: invaginations of the envelope membrane, direct contact sites between these membranes, or through vesicles. Vesicles have been observed in chloroplasts but not much is yet known about the mechanism or regulation of their formation. The question of whether proteins can also make use of vesicles as one mechanism of transport remains to be answered. Here we discuss the presence of vesicles in chloroplasts and their potential role in transporting lipids and proteins. We additionally discuss what is known about the proteins involved in the vesicle transport and the gaps in knowledge that remain to be filled.
Topics: Biological Transport; Chloroplast Proteins; Chloroplasts; Cytoplasmic Vesicles; Lipids
PubMed: 30117121
DOI: 10.1007/s11120-018-0566-0 -
Acta Neuropathologica Apr 2021The neuronal protein α-synuclein (αS) is central to the pathogenesis of Parkinson's disease and other progressive brain diseases such as Lewy body dementia and... (Review)
Review
The neuronal protein α-synuclein (αS) is central to the pathogenesis of Parkinson's disease and other progressive brain diseases such as Lewy body dementia and multiple system atrophy. These diseases, collectively referred to as 'synucleinopathies', have long been considered purely proteinopathies: diseases characterized by the misfolding of a protein into small and large aggregates mainly consisting of that protein (in this case: α-synuclein). However, recent morphological insights into Lewy bodies, the hallmark neuropathology of human synucleinopathies, suggests these lesions are also rich in vesicles and other membranous organelles. Moreover, αS physiology and pathology are both strongly associated with various aspects of intracellular vesicle trafficking and lipid biology. αS physiologically binds to synaptic and other small vesicles, and several functions of αS in regulating vesicle biology have been proposed. Familial PD-linked αS excess and missense mutations have been shown to impair vesicle trafficking and alter lipid homeostasis. On the other hand, vesicle trafficking and lipid-related genes have emerged as Parkinson's risk factors, suggesting a bidirectional relationship. The answer to the question "Does abnormal αS accumulation cause impaired vesicle trafficking and lipid dyshomeostasis or is αS aggregation the consequence of such impairments?" may be "Both". Here, we review current knowledge of the αS-lipid and αS-vesicle trafficking interplay, with a special focus on Parkinson's disease and Lewy body dementia.
Topics: Animals; Cytoplasmic Vesicles; Humans; Lipid Metabolism; Protein Aggregation, Pathological; Protein Transport; Synucleinopathies; alpha-Synuclein
PubMed: 32607605
DOI: 10.1007/s00401-020-02177-z -
Plant Physiology Mar 2018
Topics: Biological Transport; Cytoplasmic Vesicles; Golgi Apparatus; Indoleacetic Acids; Intracellular Membranes; Plant Proteins; Staining and Labeling
PubMed: 29630496
DOI: 10.1104/pp.17.01510 -
Cell Dec 2010Membrane budding is a key step in vesicular transport, multivesicular body biogenesis, and enveloped virus release. These events range from those that are primarily... (Review)
Review
Membrane budding is a key step in vesicular transport, multivesicular body biogenesis, and enveloped virus release. These events range from those that are primarily protein driven, such as the formation of coated vesicles, to those that are primarily lipid driven, such as microdomain-dependent biogenesis of multivesicular bodies. Other types of budding reside in the middle of this spectrum, including caveolae biogenesis, HIV-1 budding, and ESCRT-catalyzed multivesicular body formation. Some of these latter events involve budding away from cytosol, and this unusual topology involves unique mechanisms. This Review discusses progress toward understanding the structural and energetic bases of these different membrane-budding paradigms.
Topics: Animals; Cell Membrane Structures; Cytoplasmic Vesicles; Endosomal Sorting Complexes Required for Transport; Eukaryotic Cells; Humans
PubMed: 21145455
DOI: 10.1016/j.cell.2010.11.030 -
Acta Physiologica (Oxford, England) Feb 2018Intracellular organelles, including secretory vesicles, emerged when eukaryotic cells evolved some 3 billion years ago. The primordial organelles that evolved in Archaea... (Review)
Review
Intracellular organelles, including secretory vesicles, emerged when eukaryotic cells evolved some 3 billion years ago. The primordial organelles that evolved in Archaea were similar to endolysosomes, which developed, arguably, for specific metabolic tasks, including uptake, metabolic processing, storage and disposal of molecules. In comparison with prokaryotes, cell volume of eukaryotes increased by several orders of magnitude and vesicle traffic emerged to allow for communication between distant intracellular locations. Lysosomes, first described in 1955, a prominent intermediate of endo- and exocytotic pathways, operate virtually in all eukaryotic cells including astroglia, the most heterogeneous type of homeostatic glia in the central nervous system. Astrocytes support neuronal network activity in particular through elaborated secretion, based on a complex intracellular vesicle network dynamics. Deranged homeostasis underlies disease and astroglial vesicle traffic contributes to the pathophysiology of neurodegenerative (Alzheimer's disease, Huntington's disease), neurodevelopmental diseases (intellectual deficiency, Rett's disease) and neuroinfectious (Zika virus) disorders. This review addresses astroglial cell-autonomous vesicular traffic network, as well as its into primary and secondary vesicular network defects in diseases, and considers this network as a target for developing new therapies for neurological conditions.
Topics: Animals; Astrocytes; Cytoplasmic Vesicles; Humans
PubMed: 28665546
DOI: 10.1111/apha.12915 -
Biomolecules Aug 2020Carbohydrate-binding galectins are expressed in various tissues of multicellular organisms. They are involved in autophagy, cell migration, immune response,... (Review)
Review
Carbohydrate-binding galectins are expressed in various tissues of multicellular organisms. They are involved in autophagy, cell migration, immune response, inflammation, intracellular transport, and signaling. In recent years, novel roles of galectin-interaction with membrane components have been characterized, which lead to the formation of vesicles with diverse functions. These vesicles are part of intracellular transport pathways, belong to the cellular degradation machinery, or can be released for cell-to-cell communication. Several characteristics of galectins in the lumen or at the membrane of newly formed vesicular structures are discussed in this review and illustrate the need to fully elucidate their contributions at the molecular and structural level.
Topics: Animals; Biological Transport, Active; Cell Communication; Cytoplasmic Vesicles; Exosomes; Extracellular Vesicles; Galectins; Humans; Models, Biological; Signal Transduction; Transport Vesicles
PubMed: 32847140
DOI: 10.3390/biom10091232 -
Frontiers in Immunology 2021Archaea are prokaryotic organisms that were classified as a new domain in 1990. Archaeal cellular components and metabolites have found various applications in the... (Review)
Review
Archaea are prokaryotic organisms that were classified as a new domain in 1990. Archaeal cellular components and metabolites have found various applications in the pharmaceutical industry. Some archaeal lipids can be used to produce archaeosomes, a new family of liposomes that exhibit high stability to temperatures, pH and oxidative conditions. Additionally, archaeosomes can be efficient antigen carriers and adjuvants promoting humoral and cellular immune responses. Some archaea produce gas vesicles, which are nanoparticles released by the archaea that increase the buoyancy of the cells and facilitate an upward flotation in water columns. Purified gas vesicles display a great potential for bioengineering, due to their high stability, immunostimulatory properties and uptake across cell membranes. Both archaeosomes and archaeal gas vesicles are attractive tools for the development of novel drug and vaccine carriers to control various diseases. In this review we discuss the current knowledge on production, preparation methods and potential applications of archaeosomes and gas vesicles as carriers for vaccines. We give an overview of the traditional structures of these carriers and their modifications. A comparative analysis of both vaccine delivery systems, including their advantages and limitations of their use, is provided. Gas vesicle- and archaeosome-based vaccines may be powerful next-generation tools for the prevention and treatment of a wide variety of infectious and non-infectious diseases.
Topics: Adjuvants, Immunologic; Animals; Archaea; Cytoplasmic Vesicles; Drug Carriers; Humans; Liposomes; Nanoparticles; Vaccine Development
PubMed: 34567012
DOI: 10.3389/fimmu.2021.746235