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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 -
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 -
Biomolecules Aug 2023Autophagy is the key process by which the cell degrades parts of itself within the lysosomes. It maintains cell survival and homeostasis by removing molecules... (Review)
Review
Autophagy is the key process by which the cell degrades parts of itself within the lysosomes. It maintains cell survival and homeostasis by removing molecules (particularly proteins), subcellular organelles, damaged cytoplasmic macromolecules, and by recycling the degradation products. The selective removal or degradation of mitochondria is a particular type of autophagy called mitophagy. Various forms of cellular stress (oxidative stress (OS), hypoxia, pathogen infections) affect autophagy by inducing free radicals and reactive oxygen species (ROS) formation to promote the antioxidant response. Dysfunctional mechanisms of autophagy have been found in different respiratory diseases such as chronic obstructive lung disease (COPD) and asthma, involving epithelial cells. Several existing clinically approved drugs may modulate autophagy to varying extents. However, these drugs are nonspecific and not currently utilized to manipulate autophagy in airway diseases. In this review, we provide an overview of different autophagic pathways with particular attention on the dysfunctional mechanisms of autophagy in the epithelial cells during asthma and COPD. Our aim is to further deepen and disclose the research in this direction to stimulate the develop of new and selective drugs to regulate autophagy for asthma and COPD treatment.
Topics: Humans; Mitophagy; Autophagy; Respiration Disorders; Oxidative Stress; Asthma; Pulmonary Disease, Chronic Obstructive; Epithelial Cells; Lysosomes
PubMed: 37627282
DOI: 10.3390/biom13081217 -
Methods in Molecular Biology (Clifton,... 2022Since the discovery of autophagy genes and proteins in the early1990s, numerous previously unknown physiological and pathological functions have been discovered for...
Since the discovery of autophagy genes and proteins in the early1990s, numerous previously unknown physiological and pathological functions have been discovered for autophagy. At the same time, precise monitoring of autophagy has become important, and western blotting and fluorescence microscopy of the marker protein LC3 is widely used for this purpose. Here, we describe a modification of the widely used method, number of LC3 dots per cell. This protocol provides the proportion of vesicular LC3 staining over the total LC3 staining in the same cell. The approach is well suitable for quantification of endogenous LC3.
Topics: Autophagy; Blotting, Western; Microscopy, Fluorescence; Microtubule-Associated Proteins; Tomography, Optical
PubMed: 34972985
DOI: 10.1007/978-1-0716-2071-7_4 -
Trends in Endocrinology and Metabolism:... Sep 2019Autophagy controls cellular remodeling and quality control. Dysregulated autophagy has been implicated in several human diseases including obesity, diabetes,... (Review)
Review
Autophagy controls cellular remodeling and quality control. Dysregulated autophagy has been implicated in several human diseases including obesity, diabetes, cardiovascular disease, neurodegenerative diseases, and cancer. Current evidence has revealed that FoxO (forkhead box class O) transcription factors have a multifaceted role in autophagy regulation and dysregulation. Nuclear FoxOs transactivate genes that control the formation of autophagosomes and their fusion with lysosomes. Independently of transactivation, cytosolic FoxO proteins induce autophagy by directly interacting with autophagy proteins. Autophagy is also controlled by FoxOs through epigenetic mechanisms. Moreover, FoxO proteins can be degraded directly or indirectly by autophagy. Cutting-edge evidence is reviewed that the FoxO-autophagy axis plays a crucial role in health and disease.
Topics: Animals; Autophagy; Forkhead Transcription Factors; Humans; Neoplasms; Transcription Factors
PubMed: 31443842
DOI: 10.1016/j.tem.2019.07.009 -
Trends in Genetics : TIG Jul 2022Cellular trafficking is essential to maintain critical biological functions. Mutations in 346 genes, most of them described in the last 5 years, are associated with... (Review)
Review
Cellular trafficking is essential to maintain critical biological functions. Mutations in 346 genes, most of them described in the last 5 years, are associated with disorders of cellular trafficking. Whereas initially restricted to membrane trafficking, the recent detection of many diseases has contributed to the discovery of new biological pathways. Accordingly, we propose to redesign this rapidly growing group of diseases combining biological mechanisms and clinical presentation into the following categories: (i) membrane trafficking (including organelle-related); (ii) membrane contact sites; (iii) autophagy; (iv) cytoskeleton-related. We present the most recently described pathophysiological findings, disorders and phenotypes. Although all tissues and organs are affected, the nervous system is especially vulnerable.
Topics: Autophagy; Cytoskeleton; Organelles
PubMed: 35367088
DOI: 10.1016/j.tig.2022.02.012 -
Autophagy Feb 2022Nucleophagy, the selective subtype of autophagy that predominantly targets only a selected and (nonessential) portion of the nucleus, and rarely the nucleus in its...
Nucleophagy, the selective subtype of autophagy that predominantly targets only a selected and (nonessential) portion of the nucleus, and rarely the nucleus in its entirety, for degradation, reinforces the paradigm that nucleophagy recycling is a meticulous and highly delicate process guarded by fail-safe mechanisms. Our goal in this commentary is to encourage autophagy researchers and other scientists to explore nucleophagy blind spots and gain advanced insights into the diverse roles of this process and its selective modality as they pertain to intranuclear quality control and cellular homeostasis. Identifying and deciphering nucleophagic signaling, regulation, molecular mechanism(s) and its mediators, cargo composition and nuclear membrane dynamics under numerous physiological and/or pathological settings will provide important advances in our understanding of this critical type of organelle-selective autophagy.: INM, inner nuclear membrane; LN, late nucleophagy; mRNA, messenger RNA; NE, nuclear envelope; NL, nuclear lamina; NPC(s), nuclear pore complex(es); NVJ(s), nucleus-vacuole junction(s); ONM, outer nuclear membrane; PMN, piecemeal microautophagy of the nucleus; PND, programmed nuclear death; PNuD, programmed nuclear destruction; rDNArRNA, ribosomal DNA/RNA.
Topics: Autophagy; Cell Nucleus; DNA, Ribosomal; Microautophagy; Nuclear Envelope; Saccharomyces cerevisiae
PubMed: 34643473
DOI: 10.1080/15548627.2021.1971380 -
Genes Feb 2023Lipotoxicity is a phenomenon of lipid-induced cellular injury in nonadipose tissue. Excess of free saturated fatty acids (SFAs) contributes to hepatic injury in... (Review)
Review
Lipotoxicity is a phenomenon of lipid-induced cellular injury in nonadipose tissue. Excess of free saturated fatty acids (SFAs) contributes to hepatic injury in nonalcoholic fatty liver disease (NAFLD), which has been growing at an unprecedented rate in recent years. SFAs and their derivatives such as ceramides and membrane phospholipids have been shown to induce intrahepatic oxidative damage and ER stress. Autophagy represents a cellular housekeeping mechanism to counter the perturbation in organelle function and activation of stress signals within the cell. Several aspects of autophagy, including lipid droplet assembly, lipophagy, mitophagy, redox signaling and ER-phagy, play a critical role in mounting a strong defense against lipotoxic lipid species within the hepatic cells. This review provides a succinct overview of our current understanding of autophagy-lipotoxicity interaction and its pharmacological and nonpharmacological modulation in treating NAFLD.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Autophagy; Hepatocytes; Mitophagy; Ceramides; Fatty Acids, Nonesterified
PubMed: 36874473
DOI: 10.3390/genes14030553 -
Nature Chemical Biology Jun 2021Autophagy is implicated in a wide range of (patho)physiological processes including maintenance of cellular homeostasis, neurodegenerative disorders, aging and cancer.... (Review)
Review
Autophagy is implicated in a wide range of (patho)physiological processes including maintenance of cellular homeostasis, neurodegenerative disorders, aging and cancer. As such, small molecule autophagy modulators are in great demand, both for their ability to act as tools to better understand this essential process and as potential therapeutics. Despite substantial advances in the field, major challenges remain in the development and comprehensive characterization of probes that are specific to autophagy. In this Review, we discuss recent developments in autophagy-modulating small molecules, including the specific challenges faced in the development of activators and inhibitors, and recommend guidelines for their use. Finally, we discuss the potential to hijack the process for targeted protein degradation, an area of great importance in chemical biology and drug discovery.
Topics: Animals; Autophagy; Drug Discovery; Drug Therapy; Humans; Phagosomes; Small Molecule Libraries
PubMed: 34035513
DOI: 10.1038/s41589-021-00768-9 -
Current Opinion in Immunology Oct 2021Autophagy is a fundamental component of cell-autonomous immunity, targeting intracellular pathogens including viruses and cytosolic bacteria to lysosomes for... (Review)
Review
Autophagy is a fundamental component of cell-autonomous immunity, targeting intracellular pathogens including viruses and cytosolic bacteria to lysosomes for degradation. Genetic mutations in components of the autophagy pathway result in autoinflammatory and neurodegenerative disorders. We focus on recent developments through the newly discovered inborn errors of autophagy strictly predisposing to severe viral infections. These feature mutations in TBK1, ATG4A, MAP1LC3B2, and ATG7, leading to herpes encephalitis, recurrent lymphocytic meningitis, and paralytic poliomyelitis. We highlight how this enhances our understanding of autophagy mechanisms and its role in human viral disease. As we better understand the contribution of these genes to disease, we can aim to develop targeted therapies for enhanced infection control.
Topics: Alleles; Animals; Autophagy; Biomarkers; Communicable Diseases; Genetic Predisposition to Disease; Genetic Variation; Host Microbial Interactions; Humans; Mutation; Phenotype
PubMed: 34371322
DOI: 10.1016/j.coi.2021.07.005