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Shedding light on the function of autophagy in complicated pregnancies.

Autophagy is a conserved degradation process in eukaryotic cells that is regulated by autophagy-related genes. During autophagy, lysosomes break down cytoplasmic proteins and damaged organelles. This process plays a pivotal role in cell growth and development, protection against metabolic stress and oxidative damage, and the maintenance of cellular homeostasis through the recycling of cellular components. Pregnancy encompasses crucial events such as decidualization, embryo implantation, and fetal growth. Abnormal autophagy has been implicated in several pregnancy complications and can signific…

Critical Role of Dysregulated Autophagy in Pathophysiology of Podocytopathy.

Podocytopathies are glomerular disorders characterized by podocyte injury, typically resulting in marked proteinuria. Podocytes are highly specialized, terminally differentiated epithelial cells essential for maintaining the structural and functional integrity of the glomerular filtration barrier. Owing to constant exposure to injurious stimuli, podocytes may undergo dedifferentiation, hypertrophy, apoptosis, or necrosis. Autophagy is a key cytoprotective mechanism that enables cells to degrade and recycle damaged or unnecessary components through a multistep process involving induction, autop…

Autophagy in Melanoma: Molecular Mechanisms and Therapeutic Perspectives.

Melanoma is a malignant tumor that originates in pigment-producing cells called melanocytes. This type of cancer remains a major public health challenge due to its high metastatic potential and resistance to treatment. Autophagy is a catabolic process that enables the controlled degradation of damaged cellular organelles and unnecessary or abnormal macromolecules. Its primary function is to maintain intracellular homeostasis and cell survival. There are three main types of autophagy: macroautophagy, microautophagy and chaperone-mediated autophagy (CMA). The role of autophagy in oncogenesis is …

Crosstalk between inflammation and autophagy in CeD organoids.

Celiac disease (CeD), a small bowel disorder characterized by mucosal inflammation, villous atrophy and crypt hyperplasia, is induced by gliadin peptides in genetically predisposed individuals. Alterations in inflammation, intracellular vesicular trafficking, mTOR signalling and autophagy have been reported in the intestinal epithelium of CeD patients. The aim of this manuscript was to investigate the interplay between autophagy and inflammation in intestinal mucosa of CeD patients. Increased levels of markers related to impaired autophagic flux, mTOR pathway activation and inflammatory signal…

The interplay between autophagy and unconventional secretion in neurodegeneration.

Within neurons, the misfolding and aggregation of certain proteins has been identified as a common feature of many late-onset neurodegenerative diseases (NDs). These aggregate-prone proteins include tau (in both primary tauopathies and in Alzheimer's disease) and alpha-synuclein in Parkinson's disease. There is strong experimental evidence that the upregulation of intracellular clearance pathways (autophagy and ubiquitin-proteasome pathways) can clear aggregate-prone proteins in experimental models. When the flux through these pathways is increased, the levels of aggregate-prone proteins are r…

Claudins as signaling hubs of fibrosis, autophagy, and metabolism.

Claudins were identified in 1998 as structural and functional components of tight junction (TJ) seals between adjacent epithelial cells. Sin … ns. In this review, we discuss recent findings on claudins as drug targets in relation to fibrosis, autophagy, and metabolism, focusing specifically on their functions as signaling hubs.

Clinical and biochemical footprints of inherited disorders of autophagy.

Autophagy is an evolutionarily conserved lysosomal recycling system that integrates nutrient sensing, organelle quality control, proteostasis, cellular stress responses and metabolic adaptation. Autophagy is particularly relevant for post-mitotic tissue such as neurons, skin, and immune cells. Monogenic disorders disrupting autophagy or closely coupled endolysosomal trafficking pathways have recently emerged as a recognizable group of inherited metabolic diseases. These conditions are individually rare inborn errors of metabolism and collectively important because they bridge neurodevelopmenta…

HIV-1 Vpr is targeted for degradation by autophagy.

Autophagy is part of the innate immune arsenal to fight viruses, including HIV-1. We previously reported that HIV-1 Gag is targeted for autophagy-mediated degradation. Here, we identify HIV-1 Vpr, an important virulence factor, as an autophagy target in HIV-1 NL4-3, a lab adapted molecular clone. Notably, Vpr proteins from a collection of transmitted/founder viruses (TFVs) were resistant to autophagy. Based on this observation, we identified residues at positions 37, 45, 77, 83-86, 93-94 in NL4-3 Vpr as responsible for its susceptibility to autophagy. Importantly, differences between NL4-3 and…

Role of ESCRT pathway and autophagy in neurodegenerative diseases.

Neurodegenerative diseases are characterized by progressive neuronal dysfunction and loss resulting from impaired proteostasis and vesicular trafficking. Neurons are particularly vulnerable to these processes due to their post-mitotic nature and complex architecture. Autophagy and the endolysosomal system constitute the primary degradative pathways responsible for maintaining neuronal homeostasis. However, increasing evidence indicates that their effective function critically depends on coordination with the endosomal sorting complexes required for transport (ESCRT). Beyond their canonical rol…

TRIM21 induces selective autophagy of viruses and bacteria.

TRIM21 is an exceptionally versatile ubiquitin ligase that can be directed by antibodies to target oligomeric protein scaffolds, viral capsids, and proteopathic aggregates for intracellular degradation. How the cell degrades these typically resistant substrates remains poorly understood. To address this, we used TRIM21 viral restriction to create a genome-wide phenotypic screen for antibody-dependent capsid degradation. We identify an antimicrobial selective macroautophagy pathway in mammalian cells, which we term "antibody-directed xenophagy" (ADX). We show that this mechanism restricts struc…

Drosophila as a Model to Monitor Multi-organ Autophagy.

Autophagy is a conserved lysosome-mediated pathway essential for cellular homeostasis, development, and stress responses. The fruit fly Drosophila melanogaster serves as a powerful model for autophagy research due to its genetic tractability and conservation of human disease genes. This chapter details fluorescence microscopy-based methods to monitor autophagy in multiple tissues, including the brain, midgut, Malpighian tubules, and ovary, under nutrient-replete and starvation conditions. Autophagosome dynamics are visualized using mCherry-Atg8a, while lysosomes are detected with CathepsinL im…

Drosophila as a model to study autophagy during oogenesis.

Autophagy is an evolutionarily conserved catabolic process that is essential for maintaining cellular and developmental homeostasis in eukaryotes. Drosophila oogenesis offers a robust model for investigating the spatial and temporal regulation of autophagy within a complex developmental framework that involves cells from both germline and somatic lineages. This tightly regulated cascade of events enables the differentiation of a germline stem cell into a mature oocyte. Autophagy contributes to cellular quality control, nutrient sensing, and the regulation of developmental cell death, all of wh…

Autophagy regulation by phase separation, avidity, and wetting.

Autophagy enables cells to selectively degrade a wide range of macromolecules, and how this process achieves spatial precision within the densely packed cytosol is an active area of investigation. Recent advances suggest that phase separation provides a crucial organizational framework that converts autophagy into a spatiotemporally coordinated and self-organizing process. Biomolecular condensates formed by phase separation can create high-avidity binding platforms between autophagy receptors, scaffold proteins, and the cargo that stabilize transient molecular contacts. The formation of such c…

Inborn errors of canonical autophagy in neurodegenerative diseases.

Neurodegenerative disorders (NDDs), characterized by a progressive loss of neurons and cognitive function, are a severe burden to human health and mental fitness worldwide. A hallmark of NDDs such as Alzheimer's disease, Huntington's disease, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and prion diseases is disturbed cellular proteostasis, resulting in pathogenic deposition of aggregated protein species. Autophagy is a major cellular process maintaining proteostasis and integral to innate immune defenses that mediates lysosomal protein turnover. Defects in autophagy are thus …

Insight into Autophagy and Drug Resistance in Gastric Cancer.

Chemoresistance is a major obstacle in the treatment of gastric cancer and can contribute to poor treatment and prognosis in GC patients. Autophagy is a highly conserved degradation process, and its dysregulation is closely associated with various diseases. More and more people have realized the dual role of autophagy in the treatment resistance of GC. The activation of autophagy can enhance the chemotherapy sensitivity of GC cells, but in some cases, it increases the chemoresistance. The regulation of autophagy on GC drug resistance is reflected by its impact on cell apoptosis and metastasis.…

The Role of Autophagy Genes in Energy-Related Disorders.

Autophagy is a cellular catabolic mechanism that facilitates the degradation of cytoplasmic components, thereby restoring energy homeostasis and mitigating cellular damage. This process functions as a housekeeping system, essential for maintaining organismal viability under stressful conditions. Numerous studies have highlighted the role of autophagy in regulating various physiological processes, including metabolic pathways. Notably, certain autophagy-related genes may play a relevant role in metabolic disorders, extending beyond their involvement in the autophagic process, and may offer pote…

The Differentially Expressed Genes That Are Associated With Autophagy in Microtia.

The microtia is a congenital disease that might be simultaneously influenced by internal genetic level disorder and external hazardous substances. Since autophagy is an essential cell response to adverse conditions, its dysregulation has been found to be closely linked to a number of illnesses. In comparison, the role of genes that are related to autophagy in the pathogenesis of microtia is relatively rarely discussed. In the meanwhile, the study aims to determine the degree of expression and subsequent molecular pathways of autophagy-related genes and demonstrate the possible role autophagy m…

p97/VCP is required for piecemeal autophagy of aggresomes.

Metazoan cells adapt to the exhaustion of protein quality control (PQC) systems by sequestering aggregation-prone proteins in large, pericentriolar structures termed aggresomes. Defects in both aggresome formation and clearance affect proteostasis and have been linked to neurodegenerative diseases, but aggresome clearance pathways are still underexplored. Here we show that aggresomes comprising endogenous proteins are cleared via selective autophagy requiring the cargo receptor TAX1BP1. TAX1BP1 proximitomes reveal the presence of various PQC systems at aggresomes, including Hsp70 chaperones, t…

Autophagy in myositis, a dysregulated pathway, and a target for therapy.

Corticosteroids and immunosuppressants are the mainstay of therapy for idiopathic inflammatory myopathies (IIMs). However, a significant the … ysfunctional molecular and cellular pathways underlying IIM pathogenesis. Among these, dysregulated autophagy pathways have emerged as a promising target for therapeutic intervention. Specifically, impairments in lysosomal autophagy and mitophagy have been implicated in IIMs, and modulating these processes through targeted regulatory mechanisms may offer th …

Роль автофагии в патогенезе и лечение множественного склероза.

Автофагия - это важнейший клеточный процесс, ответственный за деградацию и рециркуляцию поврежденных или ненужных компонентов, поддержание клеточного гомеостаза и защиту от стресса. Регулирование автофагии связано с различными нейродегенеративными заболеваниями, включая множественный склероз, болезнь Альцгеймера, болезнь Паркинсона, амиотропический боковой склероз и болезнь Хантингтона. Существуют различные виды автофагии, каждая из которых имеет различные механизмы, такие, как макроаутофагия, митофагия, липофагия и автофагика с участием сопровождающих. Эти процессы необходимы для удаления ток

Совпадение в аннотации оригинала
Autophagy is a crucial cellular process responsible for the degradation and recycling of damaged or unnecessary components, maintaining cellular homeostasis and protecting against stress. Dysregulation of autophagy has been implicated in a variety of neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotroph…