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Viruses Mar 2018Present in many cell types, non-degradative secretory autophagy is a newly discovered pathway in which autophagosomes fuse with the plasma membrane instead of lysosomes.... (Review)
Review
Present in many cell types, non-degradative secretory autophagy is a newly discovered pathway in which autophagosomes fuse with the plasma membrane instead of lysosomes. Surprisingly, some viruses exploit secretory autophagy to exit cells non-lytically, shedding into the extracellular environment as particle populations contained within vesicles. As a result, this significantly enhances the infectivity of these viruses. In this paper, this novel cellular exit pathway is highlighted and its advantages for viral transmission discussed.
Topics: Animals; Autophagosomes; Autophagy; Enterovirus; Enterovirus Infections; Host-Pathogen Interactions; Humans; RNA, Viral; Virus Replication
PubMed: 29558400
DOI: 10.3390/v10030139 -
FEBS Letters Apr 2021Mitophagy is one of the selective autophagy pathways that catabolizes dysfunctional or superfluous mitochondria. Under mitophagy-inducing conditions, mitochondria are... (Review)
Review
Mitophagy is one of the selective autophagy pathways that catabolizes dysfunctional or superfluous mitochondria. Under mitophagy-inducing conditions, mitochondria are labeled with specific molecular landmarks that recruit the autophagy machinery to the surface of mitochondria, enclosed into autophagosomes, and delivered to lysosomes (vacuoles in yeast) for degradation. As damaged mitochondria are the major sources of reactive oxygen species, mitophagy is critical for mitochondrial quality control and cellular health. Moreover, appropriate control of mitochondrial quantity via mitophagy is vital for the energy supply-demand balance in cells and whole organisms, cell differentiation, and developmental programs. Thus, it seems conceivable that defects in mitophagy could elicit pleiotropic pathologies such as excess inflammation, tissue injury, neurodegeneration, and aging. In this review, we will focus on the molecular basis and physiological relevance of mitophagy, and potential of mitophagy as a therapeutic target to overcome such disorders.
Topics: Aging; Animals; Autophagosomes; Autophagy; Humans; Inflammation; Mitochondria; Mitophagy; Neurodegenerative Diseases; Reactive Oxygen Species
PubMed: 33615465
DOI: 10.1002/1873-3468.14060 -
Science Signaling Feb 2017Macroautophagy is a process in which cytoplasmic components, including whole organelles, are degraded within lysosomes. Basally, this process is essential for... (Review)
Review
Macroautophagy is a process in which cytoplasmic components, including whole organelles, are degraded within lysosomes. Basally, this process is essential for homeostasis and is constitutively functional in most cells, but it can also be implemented as part of stress responses. We discuss findings showing that autophagy proteins can modulate and amplify the activities of transcription factors involved in stress responses, such as those in the p53, FOXO, MiT/TFE, Nrf2, and NFκB/Rel families. Thus, transcription factors not only amplify stress responses and autophagy but are also subject to retrograde regulation by autophagy-related proteins. Physical interactions with autophagy-related proteins, competition for activating intermediates, and "signalphagy," which is the role autophagy plays in the degradation of specific signaling proteins, together provide powerful tools for implementing negative feedback or positive feed-forward loops on the transcription factors that regulate autophagy. We present examples illustrating how this network interacts to regulate metabolic and physiologic responses.
Topics: Animals; Autophagosomes; Autophagy; Humans; Lysosomes; Models, Biological; Protein Interaction Maps; Signal Transduction; Stress, Physiological; Transcription Factors
PubMed: 28246201
DOI: 10.1126/scisignal.aag2791 -
The EMBO Journal Apr 2022Synaptic function crucially relies on the constant supply and removal of neuronal membranes. The morphological complexity of neurons poses a significant challenge for... (Review)
Review
Synaptic function crucially relies on the constant supply and removal of neuronal membranes. The morphological complexity of neurons poses a significant challenge for neuronal protein transport since the machineries for protein synthesis and degradation are mainly localized in the cell soma. In response to this unique challenge, local micro-secretory systems have evolved that are adapted to the requirements of neuronal membrane protein proteostasis. However, our knowledge of how neuronal proteins are synthesized, trafficked to membranes, and eventually replaced and degraded remains scarce. Here, we review recent insights into membrane trafficking at synaptic sites and into the contribution of local organelles and micro-secretory pathways to synaptic function. We describe the role of endoplasmic reticulum specializations in neurons, Golgi-related organelles, and protein complexes like retromer in the synthesis and trafficking of synaptic transmembrane proteins. We discuss the contribution of autophagy and of proteasome-mediated and endo-lysosomal degradation to presynaptic proteostasis and synaptic function, as well as nondegradative roles of autophagosomes and lysosomes in signaling and synapse remodeling. We conclude that the complexity of neuronal cyto-architecture necessitates long-distance protein transport that combines degradation with signaling functions.
Topics: Autophagosomes; Autophagy; Endoplasmic Reticulum; Lysosomes; Proteostasis; Synapses
PubMed: 35285533
DOI: 10.15252/embj.2021110057 -
Autophagy 2018The membrane origins of autophagosomes have been a key unresolved question in the field. The earliest morphologically recognizable structure in the...
The membrane origins of autophagosomes have been a key unresolved question in the field. The earliest morphologically recognizable structure in the macroautophagy/autophagy itinerary is the double-membraned cup-shaped phagophore. Newly formed phosphatidylinositol 3-phosphate (PtdIns3P) on the membranes destined to become phagophores recruits WIPI2, which, in turn, binds ATG16L1 to define the sites of autophagosome formation. Here we review our recent study showing that membrane recruitment of WIPI2 requires coincident detection of PtdIns3P and RAB11A, a protein that marks recycling endosomes. We found that multiple core autophagy proteins are more tightly associated with the recycling endosome compartment than with endoplasmic reticulum (ER)-mitochondrial contact sites. Furthermore, biochemical isolation of the recycling endosomes confirmed that they recruit autophagy proteins. Finally, fixed and live-cell imaging data revealed that recycling endosomes engulf autophagic substrates. Indeed, the sequestration of mitochondria after mitophagy stimulation depends on early autophagy regulators. These data suggest that autophagosomes evolve from the RAB11A compartment.
Topics: Autophagosomes; Autophagy; Carrier Proteins; Endosomes; Membrane Proteins; Protein Transport
PubMed: 29940791
DOI: 10.1080/15548627.2018.1482148 -
Seminars in Cell & Developmental Biology Dec 2016Autophagy, a conserved self-eating process for the bulk degradation of cytoplasmic materials, involves double-membrane autophagosomes formed when an isolation membrane... (Review)
Review
Autophagy, a conserved self-eating process for the bulk degradation of cytoplasmic materials, involves double-membrane autophagosomes formed when an isolation membrane emerges and their direct fusion with lysosomes for degradation. For the early biogenesis of autophagosomes and their later degradation in lysosomes, membrane fusion is necessary, although different sets of genes and autophagy-related proteins involved in distinct fusion steps have been reported. To clarify the molecular mechanism of membrane fusion in autophagy, to not only expand current knowledge of autophagy, but also benefit human health, this review discusses key findings that elucidate the unique membrane dynamics of autophagy.
Topics: Animals; Autophagosomes; Autophagy; Autophagy-Related Proteins; Humans; Membrane Fusion; SNARE Proteins
PubMed: 27422330
DOI: 10.1016/j.semcdb.2016.07.009 -
FEBS Letters Sep 2022Plant selective (macro)autophagy is a highly regulated process where eukaryotic cells spatiotemporally degrade some of their constituents that have become superfluous or... (Review)
Review
Plant selective (macro)autophagy is a highly regulated process where eukaryotic cells spatiotemporally degrade some of their constituents that have become superfluous or harmful. The identification and characterization of the factors determining this selectivity make it possible to integrate selective (macro)autophagy into plant cell physiology and homeostasis. The specific cargo receptors and/or scaffold proteins involved in this pathway are generally not structurally conserved, as are the biochemical mechanisms underlying recognition and integration of a given cargo into the autophagosome in different cell types. This review discusses the few specific cargo receptors described in plant cells to highlight key features of selective autophagy in the plant kingdom and its integration with plant physiology, aiming to identify evolutionary convergence and knowledge gaps to be filled by future research.
Topics: Autophagosomes; Autophagy; Homeostasis; Plant Cells
PubMed: 35638898
DOI: 10.1002/1873-3468.14412 -
IUBMB Life Apr 2022Organelles can easily be disrupted by intracellular and extracellular factors. Studies on ER and mitochondria indicate that a wide range of responses are elicited upon...
Organelles can easily be disrupted by intracellular and extracellular factors. Studies on ER and mitochondria indicate that a wide range of responses are elicited upon organelle disruption. One response thought to be of particular importance is autophagy. Cells can target entire organelles into autophagosomes for removal. This wholesale nature makes autophagy a robust means for eliminating compromised organelles. Recently, it was demonstrated that the Golgi apparatus is a substrate of autophagy. On the other hand, various reports have shown that components traffic away from the Golgi for elimination in an autophagosome-independent manner when the Golgi apparatus is stressed. Future studies will reveal how these different pieces of machinery coordinate to drive Golgi degradation. Quantitative measurements will be needed to determine how much autophagy contributes to the maintenance of the Golgi apparatus.
Topics: Autophagosomes; Autophagy; Endoplasmic Reticulum; Golgi Apparatus; Quality Control
PubMed: 35274438
DOI: 10.1002/iub.2611 -
Journal of Molecular Medicine (Berlin,... Nov 2016Autophagy is a major degradation pathway that engulfs, removes, and recycles unwanted cytoplasmic material including damaged organelles and toxic protein aggregates. One... (Review)
Review
Autophagy is a major degradation pathway that engulfs, removes, and recycles unwanted cytoplasmic material including damaged organelles and toxic protein aggregates. One type of autophagy, macroautophagy, is a tightly regulated process facilitated by autophagy-related (Atg) proteins that must communicate effectively and act in concert to enable the de novo formation of the phagophore, its maturation into an autophagosome, and its subsequent targeting and fusion with the lysosome or the vacuole. Autophagy plays a significant role in physiology, and its dysregulation has been linked to several diseases, which include certain cancers, cardiomyopathies, and neurodegenerative diseases. Here, we summarize the key processes and the proteins that make up the macroautophagy machinery. We also briefly highlight recently uncovered molecular mechanisms specific to neurons allowing them to uniquely regulate this catabolic process to accommodate their complicated architecture and non-dividing state. Overall, these distinct mechanisms establish a conceptual framework addressing how macroautophagic dysfunction could result in maladies of the nervous system, providing possible therapeutic avenues to explore with a goal of preventing or curing such diseases.
Topics: Animals; Autophagosomes; Autophagy; Humans; Membrane Fusion; Models, Biological; Neurons
PubMed: 27544281
DOI: 10.1007/s00109-016-1461-9 -
Cells May 2023Physiologically, autophagy is an evolutionarily conserved and self-degradative process in cells. Autophagy carries out normal physiological roles throughout mammalian... (Review)
Review
Physiologically, autophagy is an evolutionarily conserved and self-degradative process in cells. Autophagy carries out normal physiological roles throughout mammalian life. Accumulating evidence shows autophagy as a mechanism for cellular growth, development, differentiation, survival, and homeostasis. In male reproductive systems, normal spermatogenesis and steroidogenesis need a balance between degradation and energy supply to preserve cellular metabolic homeostasis. The main process of autophagy includes the formation and maturation of the phagophore, autophagosome, and autolysosome. Autophagy is controlled by a group of autophagy-related genes that form the core machinery of autophagy. Three types of autophagy mechanisms have been discovered in mammalian cells: macroautophagy, microautophagy, and chaperone-mediated autophagy. Autophagy is classified as non-selective or selective. Non-selective macroautophagy randomly engulfs the cytoplasmic components in autophagosomes that are degraded by lysosomal enzymes. While selective macroautophagy precisely identifies and degrades a specific element, current findings have shown the novel functional roles of autophagy in male reproduction. It has been recognized that dysfunction in the autophagy process can be associated with male infertility. Overall, this review provides an overview of the cellular and molecular basics of autophagy and summarizes the latest findings on the key role of autophagy in mammalian male reproductive physiology.
Topics: Animals; Male; Macroautophagy; Autophagy; Autophagosomes; Microautophagy; Lysosomes; Mammals
PubMed: 37174722
DOI: 10.3390/cells12091322