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EMBO Reports Sep 2023Over the recent years, it has become apparent that a deeper understanding of cell-to-cell and organ-to-organ communication is necessary to fully comprehend both... (Review)
Review
Over the recent years, it has become apparent that a deeper understanding of cell-to-cell and organ-to-organ communication is necessary to fully comprehend both homeostatic and pathological states. Autophagy is indispensable for cellular development, function, and homeostasis. A crucial aspect is that autophagy can also mediate these processes through its secretory role. The autophagy-derived secretome relays its extracellular signals in the form of nutrients, proteins, mitochondria, and extracellular vesicles. These crosstalk mediators functionally shape cell fate decisions, tissue microenvironment and systemic physiology. The diversity of the secreted cargo elicits an equally diverse type of responses, which span over metabolic, inflammatory, and structural adaptations in disease and homeostasis. We review here the emerging role of the autophagy-derived secretome in the communication between different cell types and organs and discuss the mechanisms involved.
Topics: Cell Communication; Autophagy; Extracellular Vesicles; Biological Transport; Proteins
PubMed: 37465980
DOI: 10.15252/embr.202357289 -
Essays in Biochemistry 2013Autophagy is intimately associated with eukaryotic cell death and apoptosis. Indeed, in some cases the same proteins control both autophagy and apoptosis. Apoptotic... (Review)
Review
Autophagy is intimately associated with eukaryotic cell death and apoptosis. Indeed, in some cases the same proteins control both autophagy and apoptosis. Apoptotic signalling can regulate autophagy and conversely autophagy can regulate apoptosis (and most likely other cell death mechanisms). However, the molecular connections between autophagy and cell death are complicated and, in different contexts, autophagy may promote or inhibit cell death. Surprisingly, although we know that, at its core, autophagy involves degradation of sequestered cytoplasmic material, and therefore presumably must be mediating its effects on cell death by degrading something, in most cases we have little idea of what is being degraded to promote autophagy's pro- or anti-death activities. Because autophagy is known to play important roles in health and many diseases, it is critical to understand the mechanisms by which autophagy interacts with and affects the cell death machinery since this will perhaps allow new ways to prevent or treat disease. In the present chapter, we discuss the current state of understanding of these processes.
Topics: Animals; Apoptosis; Autophagy; Humans; Signal Transduction
PubMed: 24070475
DOI: 10.1042/bse0550105 -
The Journal of Biological Chemistry Jul 2022Autophagy is an essential cellular process involving degradation of superfluous or defective macromolecules and organelles as a form of homeostatic recycling. Initially... (Review)
Review
Autophagy is an essential cellular process involving degradation of superfluous or defective macromolecules and organelles as a form of homeostatic recycling. Initially proposed to be a "bulk" degradation pathway, a more nuanced appreciation of selective autophagy pathways has developed in the literature in recent years. As a glycogen-selective autophagy process, "glycophagy" is emerging as a key metabolic route of transport and delivery of glycolytic fuel substrate. Study of glycophagy is at an early stage. Enhanced understanding of this major noncanonical pathway of glycogen flux will provide important opportunities for new insights into cellular energy metabolism. In addition, glycogen metabolic mishandling is centrally involved in the pathophysiology of several metabolic diseases in a wide range of tissues, including the liver, skeletal muscle, cardiac muscle, and brain. Thus, advances in this exciting new field are of broad multidisciplinary interest relevant to many cell types and metabolic states. Here, we review the current evidence of glycophagy involvement in homeostatic cellular metabolic processes and of molecular mediators participating in glycophagy flux. We integrate information from a variety of settings including cell lines, primary cell culture systems, ex vivo tissue preparations, genetic disease models, and clinical glycogen disease states.
Topics: Autophagy; Glycogen; Glycogenolysis; Macroautophagy
PubMed: 35654138
DOI: 10.1016/j.jbc.2022.102093 -
Cells Nov 2023Autophagy is an essential lysosome-mediated degradation pathway that maintains cellular homeostasis and viability in response to various intra- and extracellular... (Review)
Review
Autophagy is an essential lysosome-mediated degradation pathway that maintains cellular homeostasis and viability in response to various intra- and extracellular stresses. Mitophagy is a type of autophagy that is involved in the intricate removal of dysfunctional mitochondria during conditions of metabolic stress. In this review, we describe the multifaceted roles of autophagy and mitophagy in normal physiology and the field of cancer biology. Autophagy and mitophagy exhibit dual context-dependent roles in cancer development, acting as tumor suppressors and promoters. We also discuss the important role of autophagy and mitophagy within the cancer microenvironment and how autophagy and mitophagy influence tumor host-cell interactions to overcome metabolic deficiencies and sustain the activity of cancer-associated fibroblasts (CAFs) in a stromal environment. Finally, we explore the dynamic interplay between autophagy and the immune response in tumors, indicating their potential as immunomodulatory targets in cancer therapy. As the field of autophagy and mitophagy continues to evolve, this comprehensive review provides insights into their important roles in cancer and cancer microenvironment.
Topics: Humans; Mitophagy; Autophagy; Neoplasms; Biology; Tumor Microenvironment
PubMed: 38067169
DOI: 10.3390/cells12232742 -
Journal of Innate Immunity 2013
Topics: Animals; Autophagy; Humans; Immunity, Innate
PubMed: 23774622
DOI: 10.1159/000353153 -
Current Opinion in Critical Care Aug 2023Critical illness imposes a severe insult on the body, with various stressors triggering pronounced cell damage. This compromises cellular function, leading to a high... (Review)
Review
PURPOSE OF REVIEW
Critical illness imposes a severe insult on the body, with various stressors triggering pronounced cell damage. This compromises cellular function, leading to a high risk of multiple organ failure. Autophagy can remove damaged molecules and organelles but appears insufficiently activated during critical illness. This review discusses insight into the role of autophagy in critical illness and the involvement of artificial feeding in insufficient autophagy activation in critical illness.
RECENT FINDINGS
Animal studies manipulating autophagy have shown its protective effects against kidney, lung, liver, and intestinal injury after several critical insults. Autophagy activation also protected peripheral, respiratory, and cardiac muscle function, despite aggravated muscle atrophy. Its role in acute brain injury is more equivocal. Animal and patient studies showed that artificial feeding suppressed autophagy activation in critical illness, particularly with high protein/amino acid doses. Feeding-suppressed autophagy may explain short and long-term harm by early enhanced calorie/protein feeding in large randomized controlled trials.
SUMMARY
Insufficient autophagy during critical illness is at least partly explained by feeding-induced suppression. This may explain why early enhanced nutrition failed to benefit critically ill patients or even induced harm. Safe, specific activation of autophagy avoiding prolonged starvation opens perspectives for improving outcomes of critical illness.
Topics: Animals; Humans; Critical Illness; Autophagy; Nutritional Support; Nutritional Status; Liver
PubMed: 37306474
DOI: 10.1097/MCC.0000000000001056 -
Viruses May 2021Selective autophagy has emerged as a key mechanism of quality and quantity control responsible for the autophagic degradation of specific subcellular organelles and... (Review)
Review
Selective autophagy has emerged as a key mechanism of quality and quantity control responsible for the autophagic degradation of specific subcellular organelles and materials. In addition, a specific type of selective autophagy (xenophagy) is also activated as a line of defense against invading intracellular pathogens, such as viruses. However, viruses have evolved strategies to counteract the host's antiviral defense and even to activate some proviral types of selective autophagy, such as mitophagy, for their successful infection and replication. This review discusses the current knowledge on the regulation of selective autophagy by human herpesviruses.
Topics: Autophagy; Gene Expression Regulation; Herpesviridae; Host-Pathogen Interactions; Humans; Macroautophagy; Mitophagy
PubMed: 34062931
DOI: 10.3390/v13050820 -
Biomedicine & Pharmacotherapy =... Feb 2020Astrocytes can serve multiple functions in maintaining cellular homeostasis of the central nervous system (CNS), and normal functions for autophagy in astrocytes is... (Review)
Review
Astrocytes can serve multiple functions in maintaining cellular homeostasis of the central nervous system (CNS), and normal functions for autophagy in astrocytes is considered to have very vital roles in the pathogenesis of aging and neurodegenerative diseases. Autophagy is a major intracellular lysosomal (or its yeast analog, vacuolar) clearance pathways involved in the degradation and recycling of long-lived proteins, oxidatively damaged proteins and dysfunctional organelles by lysosomes. Current evidence has shown that autophagy might influence inflammation, oxidative stress, aging and function of astrocytes. Although the interrelation between autophagy and inflammation, oxidative stress, aging or neurological disorders have been addressed in detail, the influence of astrocytes mediated-autophagy in aging and neurodegenerative disorders has yet to be fully reviewed. In this review, we will summarize the most up-to-date findings and highlight the role of autophagy in astrocytes and link autophagy of astrocytes to aging and neurodegenerative diseases. Due to the prominent roles of astrocytic autophagy in age-related neurodegenerative diseases, we believe that we can provide new suggestions for the treatment of these disorders.
Topics: Aging; Animals; Astrocytes; Autophagy; Humans; Inflammation; Lysosomes; Mitophagy; Neurodegenerative Diseases; Oxidative Stress
PubMed: 31786465
DOI: 10.1016/j.biopha.2019.109691 -
Experimental Eye Research Dec 2022The cornea and covering tear film are together the 'objective lens' of the eye through which 80% of light is refracted. Despite exposure to a physically harsh and at... (Review)
Review
The cornea and covering tear film are together the 'objective lens' of the eye through which 80% of light is refracted. Despite exposure to a physically harsh and at times infectious or toxic environment, transparency essential for sight is in most cases maintained. Such resiliency makes the avascular cornea a superb model for the exploration of autophagy in the regulation of homeostasis with relevancy to all organs. Nonetheless, missense mutations and inflammation respectively clog or apparently overwhelm autophagic flux to create dystrophies much like in neurodegenerative diseases or further exacerbate inflammation. Here there is opportunity to generate novel topical therapies towards the restoration of homeostasis with potential broad application.
Topics: Humans; Cornea; Tears; Autophagy; Lens, Crystalline; Inflammation
PubMed: 36252655
DOI: 10.1016/j.exer.2022.109274 -
International Journal of Molecular... Sep 2023The heat shock factor 1 (HSF1)-mediated stress response pathway and autophagy processes play important roles in the maintenance of proteostasis. Autophagy processes are... (Review)
Review
The heat shock factor 1 (HSF1)-mediated stress response pathway and autophagy processes play important roles in the maintenance of proteostasis. Autophagy processes are subdivided into three subtypes: macroautophagy, chaperone-mediated autophagy (CMA), and microautophagy. Recently, molecular chaperones and co-factors were shown to be involved in the selective degradation of substrates by these three autophagy processes. This evidence suggests that autophagy processes are regulated in a coordinated manner by the HSF1-mediated stress response pathway. Recently, various studies have demonstrated that proteostasis pathways including HSF1 and autophagy are implicated in longevity. Furthermore, they serve as therapeutic targets for aging-related diseases such as cancer and neurodegenerative diseases. In the future, these studies will underpin the development of therapies against various diseases.
Topics: Autophagy; Macroautophagy; Chaperone-Mediated Autophagy; Microautophagy; Longevity
PubMed: 37762105
DOI: 10.3390/ijms241813804