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Annual Review of Pharmacology and... Jan 2017Macroautophagy (hereafter called autophagy) is a vacuolar, lysosomal pathway for catabolism of intracellular material that is conserved among eukaryotic cells. Autophagy... (Review)
Review
Macroautophagy (hereafter called autophagy) is a vacuolar, lysosomal pathway for catabolism of intracellular material that is conserved among eukaryotic cells. Autophagy plays a crucial role in tissue homeostasis, adaptation to stress situations, immune responses, and the regulation of the inflammatory response. Blockade or uncontrolled activation of autophagy is associated with cancer, diabetes, obesity, cardiovascular disease, neurodegenerative disease, autoimmune disease, infection, and chronic inflammatory disease. During the past decade, researchers have made major progress in understanding the three levels of regulation of autophagy in mammalian cells: signaling, autophagosome formation, and autophagosome maturation and lysosomal degradation. As we discuss in this review, each of these levels is potentially druggable, and, depending on the indication, may be able to stimulate or inhibit autophagy. We also summarize the different modulators of autophagy and their potential and limitations in the treatment of life-threatening diseases.
Topics: Animals; Autophagy; Clinical Trials as Topic; Humans; Lysosomes; Neoplasms; Neurodegenerative Diseases; Signal Transduction; Sirolimus
PubMed: 28061686
DOI: 10.1146/annurev-pharmtox-010716-104936 -
Future Microbiology Sep 2023HSV can evade host defenses and cause lifelong infection and severe illness. Lysosomes are catabolic organelles that play an important role in the regulation of... (Review)
Review
HSV can evade host defenses and cause lifelong infection and severe illness. Lysosomes are catabolic organelles that play an important role in the regulation of cellular homeostasis. Lysosomal dysfunction and alterations in the process of autophagy have been identified in a variety of diseases, including HSV infection, and targeting lysosomes is a potential anti-HSV therapeutic strategy. This article reviews the role of lysosomes and lysosome-associated proteins in HSV infection, providing attractive targets and novel strategies for the treatment of HSV infection.
Topics: Homeostasis; Autophagy; Lysosomes
PubMed: 37584568
DOI: 10.2217/fmb-2023-0090 -
Drug Discovery Today Nov 2023Recently, targeted protein degradation technologies based on lysosomal pathways have been developed. Lysosome-based targeted protein degradation technology has a broad... (Review)
Review
Recently, targeted protein degradation technologies based on lysosomal pathways have been developed. Lysosome-based targeted protein degradation technology has a broad range of substrates and the potential to degrade intracellular and extracellular proteins, protein aggregates, damaged organelles and non-protein molecules. Thus, they hold great promise for drug R&D. This study has focused on the biogenesis of lysosomes, their basic functions, lysosome-associated diseases and targeted protein degradation technologies through the lysosomal pathway. In addition, we thoroughly examine the potential applications and limitations of this technology and engage in insightful discussions on potential avenues for future research. Our primary objective is to foster preclinical research on this technology and facilitate its successful clinical implementation.
Topics: Proteolysis; Lysosomes; Proteins; Autophagy
PubMed: 37708931
DOI: 10.1016/j.drudis.2023.103767 -
Journal of Trace Elements in Medicine... Dec 2020Autophagy is a conserved catabolic process that plays an important role in cellular homeostasis. The study of the interplay between autophagy and zinc has gained... (Review)
Review
Autophagy is a conserved catabolic process that plays an important role in cellular homeostasis. The study of the interplay between autophagy and zinc has gained interest over the last years. Multiple studies have indicated that zinc stimulates autophagy and is critical for basal and induced autophagy in mammalian cells. Conversely, autophagy is induced by zinc starvation in yeast. There are no studies analyzing the role of zinc in either Microautophagy or Chaperone-Mediated-Autophagy. The mechanisms by which zinc modulates autophagy are still poorly understood. Studies examining loss of function of genes involved in cellular zinc homeostasis have provided novel insights into the role of zinc in autophagy. Autophagy may help cells adapt to changes in zinc availability in medium by controlling zinc mobilization, recycling, and secretion. Zinc is a key player in toxic and protective autophagy.
Topics: Animals; Autophagy; Humans; Lysosomes; Metallothionein; Mitophagy; Zinc
PubMed: 32957075
DOI: 10.1016/j.jtemb.2020.126636 -
The Journal of Biological Chemistry Apr 2018Ubiquitination is a widespread post-translational modification that controls multiple steps in autophagy, a major lysosome-mediated intracellular degradation pathway. A... (Review)
Review
Ubiquitination is a widespread post-translational modification that controls multiple steps in autophagy, a major lysosome-mediated intracellular degradation pathway. A variety of ubiquitin chains are attached as selective labels on protein aggregates and dysfunctional organelles, thus promoting their autophagy-dependent degradation. Moreover, ubiquitin modification of autophagy regulatory components is essential to positively or negatively regulate autophagy flux in both non-selective and selective pathways. We review the current findings that elucidate the components, timing, and kinetics of the multivalent role of ubiquitin signals in control of amplitude and selectivity of autophagy pathways as well as their impact on the development of human diseases.
Topics: Animals; Humans; Lysosomes; Protein Aggregates; Proteolysis; Signal Transduction; Ubiquitin; Ubiquitination
PubMed: 29187595
DOI: 10.1074/jbc.TM117.000117 -
Journal of Leukocyte Biology Nov 2023Lysosomal compartments undergo extensive remodeling during dendritic cell (DC) activation to meet the dynamic functional requirements of DCs. Instead of being regarded... (Review)
Review
Lysosomal compartments undergo extensive remodeling during dendritic cell (DC) activation to meet the dynamic functional requirements of DCs. Instead of being regarded as stationary and digestive organelles, recent studies have increasingly appreciated the versatile roles of lysosomes in regulating key aspects of DC biology. Lysosomes actively control DC motility by linking calcium efflux to the actomyosin contraction, while enhanced DC lysosomal membrane permeability contributes to the inflammasome activation. Besides, lysosomes provide a platform for the transduction of innate immune signaling and the intricate host-pathogen interplay. Lysosomes and lysosome-associated structures are also critically engaged in antigen presentation and cross-presentation processes, which are pivotal for the induction of antigen-specific adaptive immune response. Through the current review, we emphasize that lysosome targeting strategies serve as vital DC-based immunotherapies in fighting against tumor, infectious diseases, and autoinflammatory disorders.
Topics: Dendritic Cells; Antigen Presentation; Cross-Priming; Signal Transduction; Lysosomes
PubMed: 37774493
DOI: 10.1093/jleuko/qiad117 -
Biochemistry. Biokhimiia Jan 2024Autophagy is the process by which cell contents, such as aggregated proteins, dysfunctional organelles, and cell structures are sequestered by autophagosome and... (Review)
Review
Autophagy is the process by which cell contents, such as aggregated proteins, dysfunctional organelles, and cell structures are sequestered by autophagosome and delivered to lysosomes for degradation. As a process that allows the cell to get rid of non-functional components that tend to accumulate with age, autophagy has been associated with many human diseases. In this regard, the search for autophagy activators and the study of their mechanism of action is an important task for treatment of many diseases, as well as for increasing healthy life expectancy. Plants are rich sources of autophagy activators, containing large amounts of polyphenolic compounds in their composition, which can be autophagy activators in their original form, or can be metabolized by the intestinal microbiota to active compounds. This review is devoted to the plant-based autophagy activators with emphasis on the sources of their production, mechanism of action, and application in various diseases. The review also describes companies commercializing natural autophagy activators.
Topics: Humans; Autophagy; Plants; Lysosomes
PubMed: 38467543
DOI: 10.1134/S0006297924010012 -
Trends in Molecular Medicine Jan 2020Cellular function requires coordination between different organelles and metabolic cues. Mitochondria and lysosomes are essential for cellular metabolism as major... (Review)
Review
Cellular function requires coordination between different organelles and metabolic cues. Mitochondria and lysosomes are essential for cellular metabolism as major contributors of chemical energy and building blocks. It is therefore pivotal for cellular function to coordinate the metabolic roles of mitochondria and lysosomes. However, these organelles do more than metabolism, given their function as fundamental signaling platforms in the cell that regulate many key processes such as autophagy, proliferation, and cell death. Mechanisms of crosstalk between mitochondria and lysosomes are discussed, both under physiological conditions and in diseases that affect these organelles.
Topics: Animals; Autophagy; Cell Death; Cell Proliferation; Humans; Lysosomes; Metabolic Networks and Pathways; Mitochondria; Neurodegenerative Diseases; Signal Transduction
PubMed: 31791731
DOI: 10.1016/j.molmed.2019.10.009 -
Trends in Cell Biology Aug 2019Lysosomes are acidic and degradative organelles that receive and digest a plethora of molecular and particulate cargo delivered by endocytosis, autophagy, and... (Review)
Review
Lysosomes are acidic and degradative organelles that receive and digest a plethora of molecular and particulate cargo delivered by endocytosis, autophagy, and phagocytosis. The mechanisms responsible for sorting, transporting, and ultimately delivering membranes and cargo to lysosomes through fusion have been intensely investigated. Much less is understood about lysosome fission, which is necessary to balance the incessant flow of cargo into lysosomes and maintain steady-state number, size, and function of lysosomes. Here, we review the emerging picture of how lipid signals, coat and adaptor proteins, and motor-cytoskeletal assemblies drive budding, tubulation, splitting, and 'kiss-and-run' events that enable fission and exit from lysosomes and related organelles.
Topics: Animals; Humans; Lysosomes
PubMed: 31171420
DOI: 10.1016/j.tcb.2019.05.003 -
Frontiers in Immunology 2021Autophagy is a vital conserved degradative process that maintains cellular homeostasis by recycling or eliminating dysfunctional cellular organelles and proteins. More... (Review)
Review
Autophagy is a vital conserved degradative process that maintains cellular homeostasis by recycling or eliminating dysfunctional cellular organelles and proteins. More recently, autophagy has become a well-recognized host defense mechanism against intracellular pathogens through a process known as xenophagy. On the host-microbe battlefield many intracellular bacterial pathogens have developed the ability to subvert xenophagy to establish infection. Obligately intracellular bacterial pathogens of the family, including , and have developed a dichotomous strategy to exploit the host autophagic pathway to obtain nutrients while escaping lysosomal destruction for intracellular survival within the host cell. In this review, the recent findings regarding how these master manipulators engage and inhibit autophagy for infection are explored. Future investigation to understand mechanisms used by to exploit autophagy may advance novel antimicrobial therapies and provide new insights into how intracellular microbes exploit autophagy to survive.
Topics: Anaplasmataceae; Anaplasmataceae Infections; Animals; Autophagy; Host Microbial Interactions; Humans; Immunity, Innate; Lysosomes; Signal Transduction; Wnt Signaling Pathway
PubMed: 33912170
DOI: 10.3389/fimmu.2021.642771