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Journal of Molecular Cell Biology Nov 2023Legionella pneumophila is a Gram-negative bacterium ubiquitously present in freshwater environments and causes a serious type of pneumonia called Legionnaires' disease.... (Review)
Review
Legionella pneumophila is a Gram-negative bacterium ubiquitously present in freshwater environments and causes a serious type of pneumonia called Legionnaires' disease. During infections, L. pneumophila releases over 300 effector proteins into host cells through an Icm/Dot type IV secretion system to manipulate the host defense system for survival within the host. Notably, certain effector proteins mediate posttranslational modifications (PTMs), serving as useful approaches exploited by L. pneumophila to modify host proteins. Some effectors catalyze the addition of host protein PTMs, while others mediate the removal of PTMs from host proteins. In this review, we summarize L. pneumophila effector-mediated PTMs of host proteins, including phosphorylation, ubiquitination, glycosylation, AMPylation, phosphocholination, methylation, and ADP-ribosylation, as well as dephosphorylation, deubiquitination, deAMPylation, deADP-ribosylation, dephosphocholination, and delipidation. We describe their molecular mechanisms and biological functions in the regulation of bacterial growth and Legionella-containing vacuole biosynthesis and in the disruption of host immune and defense machinery.
Topics: Humans; Legionella pneumophila; Legionnaires' Disease; Protein Processing, Post-Translational; Vacuoles; Ubiquitination
PubMed: 37156500
DOI: 10.1093/jmcb/mjad032 -
International Journal of Molecular... Jun 2020Nucleophagy, 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... (Review)
Review
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 vesicles.
Topics: Animals; Autophagy; Cell Nucleus; Humans; Microautophagy; Nuclear Proteins; Vacuoles
PubMed: 32599961
DOI: 10.3390/ijms21124506 -
The Plant Cell Jan 2022Endomembrane trafficking is essential for all eukaryotic cells. The best-characterized membrane trafficking organelles include the endoplasmic reticulum (ER), Golgi... (Review)
Review
Endomembrane trafficking is essential for all eukaryotic cells. The best-characterized membrane trafficking organelles include the endoplasmic reticulum (ER), Golgi apparatus, early and recycling endosomes, multivesicular body, or late endosome, lysosome/vacuole, and plasma membrane. Although historically plants have given rise to cell biology, our understanding of membrane trafficking has mainly been shaped by the much more studied mammalian and yeast models. Whereas organelles and major protein families that regulate endomembrane trafficking are largely conserved across all eukaryotes, exciting variations are emerging from advances in plant cell biology research. In this review, we summarize the current state of knowledge on plant endomembrane trafficking, with a focus on four distinct trafficking pathways: ER-to-Golgi transport, endocytosis, trans-Golgi network-to-vacuole transport, and autophagy. We acknowledge the conservation and commonalities in the trafficking machinery across species, with emphasis on diversity and plant-specific features. Understanding the function of organelles and the trafficking machinery currently nonexistent in well-known model organisms will provide great opportunities to acquire new insights into the fundamental cellular process of membrane trafficking.
Topics: Autophagy; Biological Transport; Endocytosis; Endoplasmic Reticulum; Golgi Apparatus; Plant Physiological Phenomena; Vacuoles
PubMed: 34550393
DOI: 10.1093/plcell/koab235 -
FEBS Letters Sep 2022Autophagy is a eukaryotic cellular transport mechanism that delivers intracellular macromolecules, proteins, and even organelles to a lytic organelle (vacuole in yeast... (Review)
Review
Autophagy is a eukaryotic cellular transport mechanism that delivers intracellular macromolecules, proteins, and even organelles to a lytic organelle (vacuole in yeast and plants/lysosome in animals) for degradation and nutrient recycling. The process is mediated by highly conserved autophagy-related (ATG) proteins. In plants, autophagy maintains cellular homeostasis under favorable conditions, guaranteeing normal plant growth and fitness. Severe stress such as nutrient starvation and plant senescence further induce it, thus ensuring plant survival under unfavorable conditions by providing nutrients through the removal of damaged or aged proteins, or organelles. In this article, we examine the interplay between metabolism and autophagy, focusing on the different aspects of this reciprocal relationship. We show that autophagy has a strong influence on a range of metabolic processes, whereas at the same time, even single metabolites can activate autophagy. We highlight the involvement of ATG genes in metabolism, examine the role of the macronutrients carbon and nitrogen, and various micronutrients, and take a closer look at how the interaction between autophagy and metabolism impacts on plant phenotypes and yield.
Topics: Animals; Autophagy; Carbon; Nitrogen; Plants; Vacuoles
PubMed: 35470431
DOI: 10.1002/1873-3468.14359 -
PloS One 2022Vacuoles in plants and fungi play critical roles in cell metabolism and osmoregulation. To support these functions, vacuoles change their morphology, e.g. they fragment...
Vacuoles in plants and fungi play critical roles in cell metabolism and osmoregulation. To support these functions, vacuoles change their morphology, e.g. they fragment when these organisms are challenged with draught, high salinity or metabolic stress (e.g. acetate accumulation). In turn, morphology reflects an equilibrium between membrane fusion and fission that determines size, shape and copy number. By studying Saccharomyces cerevisiae and its vacuole as models, conserved molecular mechanisms responsible for fusion have been revealed. However, a detailed understanding of vacuole fission and how these opposing processes respond to metabolism or osmoregulation remain elusive. Herein we describe a new fluorometric assay to measure yeast vacuole fission in vitro. For proof-of-concept, we use this assay to confirm that acetate, a metabolic stressor, triggers vacuole fission and show it blocks homotypic vacuole fusion in vitro. Similarly, hypertonic stress induced by sorbitol or glucose caused robust vacuole fission in vitro whilst inhibiting fusion. Using wortmannin to inhibit phosphatidylinositol (PI) -kinases or rGyp1-46 to inactivate Rab-GTPases, we show that acetate stress likely targets PI signaling, whereas osmotic stress affects Rab signaling on vacuole membranes to stimulate fission. This study sets the stage for further investigation into the mechanisms that change vacuole morphology to support cell metabolism and osmoregulation.
Topics: Acetates; Membrane Fusion; Osmotic Pressure; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Vacuoles
PubMed: 35834522
DOI: 10.1371/journal.pone.0271199 -
Trends in Cell Biology Jul 2012Eukaryotic cells must constantly degrade both intracellular and extracellular material to maintain cellular and organismal homeostasis. Two engulfment pathways,... (Review)
Review
Eukaryotic cells must constantly degrade both intracellular and extracellular material to maintain cellular and organismal homeostasis. Two engulfment pathways, autophagy and phagocytosis, contribute to the turnover of intracellular and extracellular substrates by delivering material to the lysosome. Historically these are thought to be separate pathways, but recent studies have revealed the direct participation of autophagy proteins in phagocytosis. Autophagy proteins lipidate LC3 onto phagosomes and other macroendocytic vacuole membranes, and are required for lysosomal degradation of engulfed cargo, demonstrating an autophagosome-independent role for autophagy proteins in mediating the turnover of extracellular substrates. This review discusses the biological systems in which autophagy proteins have been found to regulate lysosome fusion to non-autophagic membranes.
Topics: Animals; Autophagy; Cell Communication; Humans; Lysosomes; Proteins; Signal Transduction; Vacuoles
PubMed: 22608991
DOI: 10.1016/j.tcb.2012.04.005 -
Cells Aug 2022Recent studies have highlighted the importance of autophagy and particularly non-canonical autophagy in the development and progression of acute pancreatitis (a frequent... (Review)
Review
Recent studies have highlighted the importance of autophagy and particularly non-canonical autophagy in the development and progression of acute pancreatitis (a frequent disease with considerable morbidity and significant mortality). An important early event in the development of acute pancreatitis is the intrapancreatic activation of trypsinogen, (i.e., formation of trypsin) leading to the autodigestion of the organ. Another prominent phenomenon associated with the initiation of this disease is vacuolisation and specifically the formation of giant endocytic vacuoles in pancreatic acinar cells. These organelles develop in acinar cells exposed to several inducers of acute pancreatitis (including taurolithocholic acid and high concentrations of secretagogues cholecystokinin and acetylcholine). Notably, early trypsinogen activation occurs in the endocytic vacuoles. These trypsinogen-activating organelles undergo activation, long-distance trafficking, and non-canonical autophagy. In this review, we will discuss the role of autophagy in acute pancreatitis and particularly focus on the recently discovered LAP-like non-canonical autophagy (LNCA) of endocytic vacuoles.
Topics: Acute Disease; Autophagy; Humans; Pancreatitis; Trypsinogen; Vacuoles
PubMed: 36010591
DOI: 10.3390/cells11162514 -
The FEBS Journal Feb 2013Plant vacuoles are unique, multifunctional organelles among eukaryotes. Considerable new insights in plant vacuolar protein sorting have been obtained recently. The... (Review)
Review
Plant vacuoles are unique, multifunctional organelles among eukaryotes. Considerable new insights in plant vacuolar protein sorting have been obtained recently. The basic machinery of protein export from the endoplasmic reticulum to the Golgi and the classical route to the lytic vacuole and the protein storage vacuole shows many similarities to vacuolar/lysosomal sorting in other eukaryotes. However, as a result of its unique functions in plant defence and as a storage compartment, some plant-specific entities and sorting determinants appear to exist. The alternative post-Golgi route, as found in animals and yeast, probably exists in plants as well. Likely, adaptor protein complex 3 fulfils a central role in this route. A Golgi-independent route involving plant-specific endoplasmic reticulum bodies appears to provide sedentary organisms such as plants with extra flexibility to cope with changing environmental conditions.
Topics: Animals; Endoplasmic Reticulum; Golgi Apparatus; Humans; Plant Cells; Plant Proteins; Protein Transport; Vacuoles
PubMed: 23241209
DOI: 10.1111/febs.12092 -
Molecular Biology of the Cell Mar 2012Size and copy number of organelles are influenced by an equilibrium of membrane fusion and fission. We studied this equilibrium on vacuoles-the lysosomes of yeast....
Size and copy number of organelles are influenced by an equilibrium of membrane fusion and fission. We studied this equilibrium on vacuoles-the lysosomes of yeast. Vacuole fusion can readily be reconstituted and quantified in vitro, but it had not been possible to study fission of the organelle in a similar way. Here we present a cell-free system that reconstitutes fragmentation of purified yeast vacuoles (lysosomes) into smaller vesicles. Fragmentation in vitro reproduces physiological aspects. It requires the dynamin-like GTPase Vps1p, V-ATPase pump activity, cytosolic proteins, and ATP and GTP hydrolysis. We used the in vitro system to show that the vacuole-associated TOR complex 1 (TORC1) stimulates vacuole fragmentation but not the opposing reaction of vacuole fusion. Under nutrient restriction, TORC1 is inactivated, and the continuing fusion activity then dominates the fusion/fission equilibrium, decreasing the copy number and increasing the volume of the vacuolar compartment. This result can explain why nutrient restriction not only induces autophagy and a massive buildup of vacuolar/lysosomal hydrolases, but also leads to a concomitant increase in volume of the vacuolar compartment by coalescence of the organelles into a single large compartment.
Topics: Cell-Free System; GTP-Binding Proteins; Guanosine Triphosphate; Hydrolysis; Intracellular Membranes; Membrane Fusion; Protein Phosphatase 2; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Sirolimus; Transcription Factors; Vacuoles; Vesicular Transport Proteins
PubMed: 22238359
DOI: 10.1091/mbc.E11-08-0703 -
Oncotarget Aug 2016Cytoplasmic vacuolization (also called cytoplasmic vacuolation) is a well-known morphological phenomenon observed in mammalian cells after exposure to bacterial or viral... (Review)
Review
Cytoplasmic vacuolization (also called cytoplasmic vacuolation) is a well-known morphological phenomenon observed in mammalian cells after exposure to bacterial or viral pathogens as well as to various natural and artificial low-molecular-weight compounds. Vacuolization often accompanies cell death; however, its role in cell death processes remains unclear. This can be attributed to studying vacuolization at the level of morphology for many years. At the same time, new data on the molecular mechanisms of the vacuole formation and structure have become available. In addition, numerous examples of the association between vacuolization and previously unknown cell death types have been reported. Here, we review these data to make a deeper insight into the role of cytoplasmic vacuolization in cell death and survival.
Topics: Animals; Bacterial Infections; Bacterial Proteins; Cell Death; Cell Survival; Cytoplasm; Endoplasmic Reticulum; Endoplasmic Reticulum-Associated Degradation; Humans; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; Necrosis; Vacuoles; Virus Diseases
PubMed: 27331412
DOI: 10.18632/oncotarget.10150