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Archives of Physiology and Biochemistry Apr 2022Autophagy is an important life phenomenon in eukaryotic cells. Its main role is to remove and degrade its damaged organelles and excess biological macromolecules, and... (Review)
Review
Autophagy is an important life phenomenon in eukaryotic cells. Its main role is to remove and degrade its damaged organelles and excess biological macromolecules, and use degradation products to provide energy and rebuild the cell structure, playing an important role in maintaining cell homeostasis and cell life activities. Mitophagy is a form of macroautophagy. It has the beneficial effect of eliminating damaged mitochondria, thereby maintaining the integrity of the mitochondrial pool. Autophagy and mitophagy have a dual role in the development of cancer. On one hand, autophagy and mitophagy can maintain the normal physiological function of cells. On the other hand, excessive autophagy and mitophagy can lead to diseases. The present review introduces the mechanisms of autophagy and mitophagy, and the main related proteins, and introduce the correlation with cancers, providing a basis for the treatment of cancers through the understanding of these proteins.
Topics: Autophagy; Homeostasis; Humans; Mitochondria; Mitophagy; Neoplasms
PubMed: 31596150
DOI: 10.1080/13813455.2019.1675714 -
Current Opinion in Neurobiology Aug 2022Macroautophagy (hereafter referred to as autophagy) is an essential quality-control pathway in neurons, which face unique functional and morphological challenges in... (Review)
Review
Macroautophagy (hereafter referred to as autophagy) is an essential quality-control pathway in neurons, which face unique functional and morphological challenges in maintaining the integrity of organelles and the proteome. To overcome these challenges, neurons have developed compartment-specific pathways for autophagy. In this review, we discuss the organization of the autophagy pathway, from autophagosome biogenesis, trafficking, to clearance, in the neuron. We dissect the compartment-specific mechanisms and functions of autophagy in axons, dendrites, and the soma. Furthermore, we highlight examples of how steps along the autophagy pathway are impaired in the context of aging and neurodegenerative disease, which underscore the critical importance of autophagy in maintaining neuronal function and survival.
Topics: Aging; Autophagy; Axons; Humans; Neurodegenerative Diseases; Neurons
PubMed: 35649324
DOI: 10.1016/j.conb.2022.102554 -
Biomedicine & Pharmacotherapy =... Jun 2023The balance between cell death and cell survival is a highly coordinated process by which cells break down and remove unnecessary or harmful materials in a controlled,... (Review)
Review
The balance between cell death and cell survival is a highly coordinated process by which cells break down and remove unnecessary or harmful materials in a controlled, highly regulated, and compartmentalized manner. Cell exposure to various stresses, such as oxygen starvation, a lack of nutrients, or exposure to radiation, can initiate autophagy. Autophagy is a carefully orchestrated process with multiple steps, each regulated by specific genes and proteins. Autophagy proteins impact cellular maintenance and cell fate in response to stress, and targeting this process is one of the most promising methods of anti-tumor therapy. It is currently not fully understood how autophagy affects different types of tumor cells, which makes it challenging to predict outcomes when this process is manipulated. In this review, we will explore the mechanisms of autophagy and investigate it as a potential and promising therapeutic target for aggressive sarcomas.
Topics: Humans; Cell Death; Sarcoma; Starvation; Autophagy; Apoptosis
PubMed: 37031493
DOI: 10.1016/j.biopha.2023.114683 -
Frontiers in Cellular and Infection... 2022Autophagy is an immune homeostasis process induced by multiple intracellular and extracellular signals. Inflammation is a protective response to harmful stimuli such as... (Review)
Review
Autophagy is an immune homeostasis process induced by multiple intracellular and extracellular signals. Inflammation is a protective response to harmful stimuli such as pathogen microbial infection and body tissue damage. infection elicits both autophagy and inflammation, and dysregulation of autophagy and inflammation promotes pathology. This review focuses on the interaction between autophagy and inflammation caused by infection, aiming to elaborate on the possible mechanism involved in the interaction.
Topics: Autophagy; Homeostasis; Humans; Inflammation; Porphyromonas gingivalis
PubMed: 35846745
DOI: 10.3389/fcimb.2022.892610 -
Nature Cancer May 2023Macroautophagy is a cellular quality-control process that degrades proteins, protein aggregates and damaged organelles. Autophagy plays a fundamental role in cancer... (Review)
Review
Macroautophagy is a cellular quality-control process that degrades proteins, protein aggregates and damaged organelles. Autophagy plays a fundamental role in cancer where, in the presence of stressors (for example, nutrient starvation, hypoxia, mechanical pressure), tumor cells activate it to degrade intracellular substrates and provide energy. Cell-autonomous autophagy in tumor cells and cell-nonautonomous autophagy in the tumor microenvironment and in the host converge on mechanisms that modulate metabolic fitness, DNA integrity and immune escape and, consequently, support tumor growth. In this Review, we will discuss insights into the tumor-modulating roles of autophagy in different contexts and reflect on how future studies using physiological culture systems may help to understand the complexity and open new therapeutic avenues.
Topics: Humans; Neoplasms; Neoplastic Processes; Autophagy; Macroautophagy; Tumor Microenvironment
PubMed: 37069394
DOI: 10.1038/s43018-023-00546-7 -
MBio Aug 2023Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as the causative agent of the recent COVID-19 pandemic, continues representing one of the main health... (Review)
Review
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as the causative agent of the recent COVID-19 pandemic, continues representing one of the main health concerns worldwide. Autophagy, in addition to its role in cellular homeostasis and metabolism, plays an important part for the host antiviral immunity. However, viruses including SARS-CoV-2 have evolved diverse mechanisms to not only overcome autophagy's antiviral pressure but also manipulate its machinery in order to enhance viral replication and propagation. Here, we discuss our current knowledge on the impact that autophagy exerts on SARS-CoV-2 replication, as well as the different counteracting measures that this virus has developed to manipulate autophagy's complex machinery. Some of the elements regarding this interplay may become future therapeutic targets in the fight against SARS-CoV-2.
Topics: Humans; SARS-CoV-2; COVID-19; Pandemics; Antiviral Agents; Autophagy
PubMed: 37436071
DOI: 10.1128/mbio.01020-23 -
Antioxidants & Redox Signaling Mar 2023Autophagy is critical to cellular homeostasis. Emergence of the concept of regulated necrosis, such as necroptosis, ferroptosis, pyroptosis, and mitochondrial... (Review)
Review
Autophagy is critical to cellular homeostasis. Emergence of the concept of regulated necrosis, such as necroptosis, ferroptosis, pyroptosis, and mitochondrial membrane-permeability transition (MPT)-derived necrosis, has revolutionized the research into necrosis. Both altered autophagy and regulated necrosis contribute to major human diseases. Recent studies reveal an intricate interplay between autophagy and regulated necrosis. Understanding the interplay at the molecular level will provide new insights into the pathophysiology of related diseases. Among the three forms of autophagy, macroautophagy is better studied for its crosstalk with regulated necrosis. Macroautophagy seemingly can either antagonize or promote regulated necrosis, depending upon the form of regulated necrosis, the type of cells or stimuli, and other cellular contexts. This review will critically analyze recent advances in the molecular mechanisms governing the intricate dialogues between macroautophagy and main forms of regulated necrosis. The dual roles of autophagy, either pro-survival or pro-death characteristics, intricate the mechanistic relationship between autophagy and regulated necrosis at molecular level in various pathological conditions. Meanwhile, key components of regulated necrosis are also involved in the regulation of autophagy, which further complicates the interrelationship. Resolving the controversies over causation between altered autophagy and a specific form of regulated necrosis requires approaches that are more definitive, where rigorous evaluation of autophagic flux and the development of more reliable and specific methods to quantify each form of necrosis will be essential. The relationship between chaperone-mediated autophagy or microautophagy and regulated necrosis remains largely unstudied. 38, 550-580.
Topics: Humans; Apoptosis; Necrosis; Pyroptosis; Ferroptosis; Autophagy
PubMed: 36053716
DOI: 10.1089/ars.2022.0110 -
Drug Discovery Today Jan 2022Pancreatic ductal adenocarcinoma (PDAC) is characterized by heightened autophagy and systemic immune dysfunction. Modest improvements in clinical outcomes have been... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is characterized by heightened autophagy and systemic immune dysfunction. Modest improvements in clinical outcomes have been demonstrated in completed clinical trials targeting autophagy with combination hydroxychloroquine (HCQ) and chemotherapy. Recent mechanistic insights into the role of autophagy-dependent immune evasion have prompted the need for more precise and druggable targets of autophagy inhibition. Sequestosome-1 (SQSTM-1) is a multidomain scaffold protein with well-established roles in autophagy, tumor necrosis factor alpha (TNFα)- and NF-κB-related signaling pathways. SQSTM1 overexpression is frequently observed in PDAC, correlating with clinical stage and outcome. Given the unique molecular structure of SQSTM-1 and its diverse activity, identifying means of limiting SQSTM-1-dependent autophagy to promote an effective immune response in PDAC could be a promising treatment strategy.
Topics: Autophagy; Drug Discovery; Humans; Molecular Targeted Therapy; Pancreatic Neoplasms; Sequestosome-1 Protein; Signal Transduction
PubMed: 34592447
DOI: 10.1016/j.drudis.2021.09.011 -
Advances in Experimental Medicine and... 2020Autophagy is closely related to the pathogenesis and progression of cardiovascular diseases. Autophagy may be a therapeutic target for many cardiovascular diseases. In... (Review)
Review
Autophagy is closely related to the pathogenesis and progression of cardiovascular diseases. Autophagy may be a therapeutic target for many cardiovascular diseases. In this chapter, we will summarize autophagy activators and inhibitors as potential drugs for cardiovascular diseases.
Topics: Autophagy; Cardiovascular Diseases; Disease Progression; Humans
PubMed: 32671754
DOI: 10.1007/978-981-15-4272-5_19 -
Current Molecular Pharmacology 2020Autophagy, a pathway for lysosomal-mediated cellular degradation, is a catabolic process that recycles intracellular components to maintain metabolism and survival. It... (Review)
Review
Autophagy, a pathway for lysosomal-mediated cellular degradation, is a catabolic process that recycles intracellular components to maintain metabolism and survival. It is classified into three major types: macroautophagy, microautophagy, and the chaperone-mediated autophagy (CMA). Autophagy is a dynamic and multistep process that includes four stages: nucleation, elongation, autophagosome formation, and fusion. Interestingly, the influence of autophagy in cancer development is complex and paradoxical, suppressive, or promotive in different contexts. Autophagy in cancer has been demonstrated to serve as both a tumour suppressor and promoter. Radiotherapy is a powerful and common strategy for many different types of cancer and can induce autophagy, which has been shown to modulate sensitivity of cancer to radiotherapy. However, the role of autophagy in radiation treatment is controversial. Some reports showed that the upregulation of autophagy was cytoprotective for cancer cells. Others, in contrast, showed that the induction of autophagy was advantageous. Here, we reviewed recent studies and attempted to discuss the various aspects of autophagy in response to radiotherapy of cancer. Thus, we could decrease the viability of cancer cell and increase the sensibility of cancer cells to radiation, providing a new basis for the application of autophagy in clinical tumor radiotherapy.
Topics: Adenylate Kinase; Autophagy; Carcinoma; Female; Glioblastoma; Humans; Male; Neoplasm Proteins; Neoplasms; Neoplastic Stem Cells; Organ Specificity; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Radiation Tolerance; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 31400274
DOI: 10.2174/1874467212666190809154518