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Autophagy Jan 2024Macroautophagy/autophagy is a conserved process in eukaryotes responsible for degrading unwanted or damaged macromolecules and organelles through the lysosome or vacuole...
Macroautophagy/autophagy is a conserved process in eukaryotes responsible for degrading unwanted or damaged macromolecules and organelles through the lysosome or vacuole for recycling and reutilization. Our previous studies revealed the degradation of chloroplast proteins through a pathway dependent on the ubiquitin proteasome system, known as CHLORAD. Recently, we demonstrated a role for selective autophagy in regulating chloroplast protein import and enhancing stress tolerance in plants. Specifically, we found that K63-ubiquitination of TOC components at the chloroplast outer envelope membrane is recognized by the selective autophagy adaptor NBR1, leading to the degradation of TOC proteins under UV-B irradiation and heat stresses in Arabidopsis. This process was shown to control chloroplast protein import and influence photosynthetic activity. Based on our results, we have, for the first time, demonstrated that selective autophagy plays a vital role in chloroplast protein degradation, specifically in response to certain abiotic stresses.
Topics: Macroautophagy; Autophagy; Proteins; Chloroplasts; Plants; Arabidopsis; Vacuoles; Carrier Proteins; Arabidopsis Proteins
PubMed: 37635361
DOI: 10.1080/15548627.2023.2251324 -
Trends in Microbiology May 2024In the tug-of-war between host and pathogen, both evolve to combat each other's defence arsenals. Intracellular phagosomal bacteria have developed strategies to modify... (Review)
Review
In the tug-of-war between host and pathogen, both evolve to combat each other's defence arsenals. Intracellular phagosomal bacteria have developed strategies to modify the vacuolar niche to suit their requirements best. Conversely, the host tries to target the pathogen-containing vacuoles towards the degradative pathways. The host cells use a robust system through intracellular trafficking to maintain homeostasis inside the cellular milieu. In parallel, intracellular bacterial pathogens have coevolved with the host to harbour strategies to manipulate cellular pathways, organelles, and cargoes, facilitating the conversion of the phagosome into a modified pathogen-containing vacuole (PCV). Key molecular regulators of intracellular traffic, such as changes in the organelle (phospholipid) composition, recruitment of small GTPases and associated effectors, soluble N-ethylmaleimide-sensitive factor-activating protein receptors (SNAREs), etc., are hijacked to evade lysosomal degradation. Legionella, Salmonella, Coxiella, Chlamydia, Mycobacterium, and Brucella are examples of pathogens which diverge from the endocytic pathway by using effector-mediated mechanisms to overcome the challenges and establish their intracellular niches. These pathogens extensively utilise and modulate the end processes of secretory pathways, particularly SNAREs, in repurposing the PCV into specialised compartments resembling the host organelles within the secretory network; at the same time, they avoid being degraded by the host's cellular mechanisms. Here, we discuss the recent research advances on the host-pathogen interaction/crosstalk that involves host SNAREs, conserved cellular processes, and the ongoing host-pathogen defence mechanisms in the molecular arms race against each other. The current knowledge of SNAREs, and intravacuolar bacterial pathogen interactions, enables us to understand host cellular innate immune pathways, maintenance of homeostasis, and potential therapeutic strategies to combat ever-growing antimicrobial resistance.
Topics: Host-Pathogen Interactions; Vacuoles; Humans; SNARE Proteins; Bacteria; Phagosomes; Animals; Legionella; Homeostasis
PubMed: 38040624
DOI: 10.1016/j.tim.2023.11.002 -
Trends in Parasitology Feb 2020When a malaria parasite invades a host erythrocyte it pushes itself in and invaginates a portion of the host membrane, thereby sealing itself inside and establishing... (Review)
Review
When a malaria parasite invades a host erythrocyte it pushes itself in and invaginates a portion of the host membrane, thereby sealing itself inside and establishing itself in the resulting vacuole. The parasitophorous vacuolar membrane (PVM) that surrounds the parasite is modified by the parasite, using its secretory organelles. To survive within this enveloping membrane, the organism must take in nutrients, secrete wastes, export proteins into the host cell, and eventually egress. Here, we review current understanding of the unique solutions Plasmodium has evolved to these challenges and discuss the remaining questions.
Topics: Erythrocytes; Host-Parasite Interactions; Humans; Malaria; Plasmodium; Vacuoles
PubMed: 31866184
DOI: 10.1016/j.pt.2019.11.006 -
Current Opinion in Microbiology Oct 2021During the vertebrate stage of the Plasmodium life cycle, obligate intracellular malaria parasites establish a vacuolar niche for replication, first within host... (Review)
Review
During the vertebrate stage of the Plasmodium life cycle, obligate intracellular malaria parasites establish a vacuolar niche for replication, first within host hepatocytes at the pre-patent liver-stage and subsequently in erythrocytes during the pathogenic blood-stage. Survival in this protective microenvironment requires diverse transport mechanisms that enable the parasite to transcend the vacuolar barrier. Effector proteins exported out of the vacuole modify the erythrocyte membrane, increasing access to serum nutrients which then cross the vacuole membrane through a nutrient-permeable channel, supporting rapid parasite growth. This review highlights the most recent insights into the organization of the parasite vacuole to facilitate the solute, lipid and effector protein trafficking that establishes a nutrition pipeline in the terminally differentiated, organelle-free red blood cell.
Topics: Erythrocytes; Host-Parasite Interactions; Humans; Malaria; Plasmodium; Plasmodium falciparum; Protein Transport; Protozoan Proteins; Vacuoles
PubMed: 34375857
DOI: 10.1016/j.mib.2021.07.010 -
Current Opinion in Microbiology Apr 2020Intravacuolar bacterial pathogens establish intracellular niches by constructing membrane-encompassed compartments. The vacuoles surrounding the bacteria are remarkably... (Review)
Review
Intravacuolar bacterial pathogens establish intracellular niches by constructing membrane-encompassed compartments. The vacuoles surrounding the bacteria are remarkably stable, facilitating microbial replication and preventing exposure to host cytoplasmically localized innate immune sensing mechanisms. To maintain integrity of the membrane compartment, the pathogen is armed with defensive weapons that prevent loss of vacuole integrity and potential exposure to host innate signaling. In some cases, the microbial components that maintain vacuolar integrity have been identified, but the basis for why the compartment degrades in their absence is unclear. In this review, we point out that lessons from the microbial-programmed degradation of the vacuole by the cytoplasmically localized Shigella flexneri provide crucial insights into how degradation of pathogen vacuoles occurs. We propose that in the absence of bacterial-encoded guard proteins, aberrant trafficking of host membrane-associated components results in a dysfunctional pathogen compartment. As a consequence, the vacuole is poisoned and replication is terminated.
Topics: Autophagy; Bacterial Proteins; Chlamydia trachomatis; Gram-Negative Bacteria; Host-Pathogen Interactions; Humans; Legionella pneumophila; Multiprotein Complexes; Shigella flexneri; Sorting Nexins; Vacuoles; Virulence Factors
PubMed: 32044688
DOI: 10.1016/j.mib.2020.01.008 -
Archives of Razi Institute Jun 2023(), the etiological agent of the Q fever disease, ranks among the most sporadic and persistent global public health concerns. Ruminants are the principal source of... (Review)
Review
(), the etiological agent of the Q fever disease, ranks among the most sporadic and persistent global public health concerns. Ruminants are the principal source of human infections and diseases present in both acute and chronic forms. This bacterium is an intracellular pathogen that can survive and reproduce under acidic (pH 4 to 5) and harsh circumstances that contain -containing vacuoles. By undermining the autophagy defense system of the host cell, is able to take advantage of the autophagy pathway, which allows it to improve the movement of nutrients and the membrane, thereby extending the vacuole of the reproducing bacteria. For this method to work, it requires the participation of many bacterial effector proteins. In addition, the precise and prompt identification of the causative agent of an acute disease has the potential to delay the onset of its chronic form. Moreover, to make accurate and rapid diagnoses, it is necessary to create diagnostic devices. This review summarizes the most recent research on the epidemiology, pathogenesis, and diagnosis approaches of . This study also explored the complicated relationships between and the autophagic pathway, which are essential for intracellular reproduction and survival in host cells for the infection to be effective.
Topics: Humans; Coxiella burnetii; Q Fever; Vacuoles; Autophagy
PubMed: 38028822
DOI: 10.22092/ARI.2023.361161.2636 -
Natural Product Reports Jul 2022Covering: up to 2022Plants are organic chemists par excellence and produce an amazing array of diverse chemical structures. Whereas primary metabolites are essential for... (Review)
Review
Covering: up to 2022Plants are organic chemists par excellence and produce an amazing array of diverse chemical structures. Whereas primary metabolites are essential for all living organisms and highly conserved, the specialized metabolites constitute the taxonomy-specific chemical languages that are key for fitness and survival. Allocation of plants' wide array of specialized metabolites in patterns that are fine-tuned spatiotemporally is essential for adaptation to the ever-changing environment and requires transport processes. Thus advancing our knowledge about transporters is important as also evidenced by the increasing number of transporters that control key quality traits in agriculture. In this review, we will highlight recently identified transporters and new insights related to already known transporters of plant specialized metabolites. Focus will be on the transport mechanism revealed by the biochemical characterization and how that links to its function .
Topics: Cell Membrane; Membrane Transport Proteins; Plants; Vacuoles
PubMed: 35481602
DOI: 10.1039/d2np00016d -
Trends in Microbiology Aug 2020Salmonella enterica is an important gastrointestinal and facultative intracellular pathogen. After invasion of host cells, it resides in a specialized,... (Review)
Review
Salmonella enterica is an important gastrointestinal and facultative intracellular pathogen. After invasion of host cells, it resides in a specialized, replication-permissive compartment, the Salmonella-containing vacuole (SCV). During maturation of the SCV, Salmonella remodels the host endosomal system to form a variety of membranous extensions from the SCV, one type designated Salmonella-induced filaments (SIFs). It was long unclear how Salmonella is able to sustain replication within the SCV, thought to be a nutrient-poor environment. Recent studies started to characterize the metabolic pathways used by intracellular Salmonella. Besides, new insights into the ultrastructure and biogenesis of SIFs and their essential role in nutrition were obtained lately. Here, we review the recent progress with focus on observations gained by various cellular models.
Topics: Bacterial Proteins; Cellular Microenvironment; Endosomes; Energy Metabolism; Epithelial Cells; Humans; Macrophages; Salmonella typhimurium; Type III Secretion Systems; Vacuoles
PubMed: 32345466
DOI: 10.1016/j.tim.2020.03.005 -
The Journal of Cell Biology Mar 2020Cellular adaptation in response to nutrient limitation requires the induction of autophagy and lysosome biogenesis for the efficient recycling of macromolecules. Here,...
Cellular adaptation in response to nutrient limitation requires the induction of autophagy and lysosome biogenesis for the efficient recycling of macromolecules. Here, we discovered that starvation and TORC1 inactivation not only lead to the up-regulation of autophagy and vacuole proteins involved in recycling but also result in the down-regulation of many vacuole membrane proteins to supply amino acids as part of a vacuole remodeling process. Down-regulation of vacuole membrane proteins is initiated by ubiquitination, which is accomplished by the coordination of multiple E3 ubiquitin ligases, including Rsp5, the Dsc complex, and a newly characterized E3 ligase, Pib1. The Dsc complex is negatively regulated by TORC1 through the Rim15-Ume6 signaling cascade. After ubiquitination, vacuole membrane proteins are sorted into the lumen for degradation by ESCRT-dependent microautophagy. Thus, our study uncovered a complex relationship between TORC1 inactivation and vacuole biogenesis.
Topics: Endosomal Sorting Complexes Required for Transport; Intracellular Membranes; Microautophagy; Protein Kinases; Protein Transport; Proteolysis; Repressor Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Signal Transduction; Time Factors; Transcription Factors; Ubiquitin; Ubiquitin-Protein Ligase Complexes; Ubiquitination; Vacuoles
PubMed: 32045480
DOI: 10.1083/jcb.201902127 -
Biologia Futura Mar 2022Lysosome (L), a hydrolytic compartment of the endo-lysosomal system (ELS), plays a central role in the metabolic regulation of eukaryotic cells. Furthermore, it has a... (Review)
Review
Lysosome (L), a hydrolytic compartment of the endo-lysosomal system (ELS), plays a central role in the metabolic regulation of eukaryotic cells. Furthermore, it has a central role in the cytopathology of several diseases, primarily in lysosomal storage diseases (LSDs). Mucopolysaccharidosis II (MPS II, Hunter disease) is a rare LSD caused by idunorate-2-sulphatase (IDS) enzyme deficiency. To provide a new platform for drug development and clarifying the background of the clinically observed cytopathology, we established a human in vitro model, which recapitulates all cellular hallmarks of the disease. Some of our results query the traditional concept by which the storage vacuoles originate from the endosomal system and suggest a new concept, in which endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and RAB2/LAMP positive Golgi (G) vesicles play an initiative role in the vesicle formation. In this hypothesis, Golgi is not only an indirectly affected organelle but enforced to be the main support of vacuole formation. The purposes of this minireview are to give a simple guide for understanding the main relationships in ELS, to present the storage vacuoles and their relation to ELS compartments, to recommend an alternative model for vacuole formation, and to place the Golgi in spotlight of MPS II cytopathology.
Topics: Endocytosis; Golgi Apparatus; Humans; Lysosomes; Mucopolysaccharidosis II; Vacuoles
PubMed: 34837645
DOI: 10.1007/s42977-021-00107-y