Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Autophagosomes”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

36 records · Page 2Linked to original sources
PubMed2026

Potato purple top phytoplasma infection induces autophagy-associated lipid dynamics that support pathogen proliferation.

Phytoplasmas are unculturable, phloem-restricted bacterial pathogens responsible for devastating diseases in crops and ornamentals worldwide. Their mechanism for nutrient acquisition from host plants remains largely unknown. This study demonstrated that infection with potato purple top phytoplasma induced extensive remodeling of lipid metabolism in tomato plants, closely linked to autophagy activation. Western blot and confocal analyses revealed increased ATG8 lipidation and autophagosome formation at endoplasmic reticulum stress sites, alongside the redistribution of lipid droplets toward phytoplasma cells. Lipidomic profiling showed a decline in chloroplast galactolipids and phospholipids with a concomitant rise in triacylglycerol, indicating accelerated membrane turnover and neutral lipid sequestration. Transmission electron microscopy further revealed frequent spatial proximity between lipid droplets and phytoplasmas. Inhibition of autophagy with 3-methyladenine blocked lipid droplet breakdown, disrupted endoplasmic reticulum organization, and reduced phytoplasma titers, suggesting that host autophagy contributes to phytoplasma proliferation. In addition, genome analysis identified a conserved phytoplasma-encoded alpha/beta hydrolase (potato purple top-lipase), predicted to be related to monoacylglycerol lipases. In vivo assays in yeast and Nicotiana benthamiana confirmed that potato purple top-lipase reduced neutral lipids, mainly triacylglycerol, and that catalytic triad mutations abolished activity. Because potato purple top-lipase lacks a predicted secretory signal peptide, it likely functions intracellularly within phytoplasma cells and may participate in the metabolism of lipid intermediates. These findings support a model in which phytoplasma infection is associated with host autophagy-associated lipid droplet mobilization and a phytoplasma lipase that may contribute to host-derived lipid resources, providing insight into potential nutrient acquisition strategies of phloem-restricted pathogens.

Autophagy↗
PubMed1979

A unique ultrastructural variant of Wilms' tumor. Its possible histogenetic implications.

A report of a Wilms' tumor with hitherto undescribed ultrastructural and histochemical features is presented. The unique features conform structurally, and to some extent chemically to autophagosomes, which occur in similar abundance only in granular cell myoblastoma, recently considered to be derived from neural elements. The implication of this common structural feature readdresses attention to the work of Masson, who originally theorized a neurectodermal origin for the Wilms' tumor.

Humans↗
PubMed2025

Detection of Orsay viral replication intermediates reveals spatial and regulatory links to Caenorhabditis elegans innate immune responses.

For a positive-strand RNA virus, the encoded viral RNA-dependent RNA polymerase (oRdRP) synthesizes complementary antigenome strand and uses it as a template for amplifying the viral genome, generating various replication intermediates. Structural proteins and viral genome are packaged into virions, but the fate of replication intermediates is underexplored. Here, we investigate Orsay Virus (OV) replication intermediates, including antigenome, oRdRP and double stranded RNA (dsRNA), using PCR and fluorescence-based imaging in C. elegans intestines. As for other positive-strand RNA viruses, we find that genome is in vast excess of antigenome. Antigenome is only visualized in cells when using denaturation protocols, indicating basepaired intermediates. OV antigenome is observed with distinct cytoplasmic and perinuclear localization patterns that depend on factors required for generation of primary, but not secondary, siRNAs. In both wildtype and RNA interference (RNAi) mutants, viral dsRNA is observed in the cytoplasm associated with oRdRP, suggesting cytoplasmic virus replication hubs. Additionally, using antibodies to oRdRP, we observed spherical structures of ~1μm in diameter defined by oRdRP at their surface; over 75% of infected wildtype animals show these structures, which associate with mitochondria and autophagosomes in an antiviral RNAi- and autophagy-dependent manner, respectively. Our study defines new features of OV replication intermediates in wildtype animals, setting the stage for understanding their connection to the viral life cycle and host antiviral pathways.

Journal Article↗
PubMed2025

A hypoxia-responsive tRNA-derived small RNA confers renal protection through RNA autophagy.

Transfer RNA-derived small RNAs (tsRNAs or tDRs) perform a range of cellular functions. Here, we showed that tRNA-Asp-GTC-3'tDR, a hypoxia-induced tDR derived from the 3' end of tRNA-Asp-GTC, activated autophagic flux in kidney cells and its silencing blocked autophagic flux. Functional gain-/loss-of-function studies in murine kidney disease models demonstrated a substantial renoprotective function of tRNA-Asp-GTC-3'tDR. Mechanistically, tRNA-Asp-GTC-3'tDR assembled stable G-quadruplex structures and sequestered pseudouridine synthase 7 (PUS7), preventing catalytic pseudouridylation of histone mRNAs. The resulting pseudouridylation deficiency directed histone mRNAs to the autophagosome-lysosome pathway, triggering RNA autophagy. This tDR-induced RNA autophagy pathway was activated during murine and human kidney diseases, suggesting clinical relevance. Thus, tRNA-Asp-GTC-3'tDR plays a role in regulating RNA autophagy, which helps to maintain homeostasis in kidney cells and protects against kidney injury.

Animals↗
PubMed2026

Crotonylome profiling identifies MLKL crotonylation in lupus nephritis associated with RAB1A-mTOR signalling and autophagy changes in tubular epithelial cells.

OBJECTIVE: To investigate whether MLKL crotonylation is associated with tubular autophagy-lysosome pathway homeostasis in lupus nephritis (LN) and to explore its relationship with RAB1A-mechanistic target of rapamycin (mTOR) signalling. METHODS: Crotonylome proteomics was performed in peripheral blood mononuclear cells from patients with LN, patients with systemic lupus erythematosus without nephritis and healthy controls. Renal biopsy tissues were evaluated for tubulointerstitial fibrosis and autophagy-lysosome pathway-related markers. Mechanistic studies were conducted in lipopolysaccharide-stimulated HK-2 cells. Autophagic flux was assessed using bafilomycin A1. The dependency of mTOR/autophagy changes on RAB1A was tested by siRNA-mediated knockdown. RESULTS: MLKL was identified as a differentially crotonylated protein in LN, with increased crotonylation at K95 and K219. Kidney tissues from patients with LN showed increased fibronectin and collagen III deposition compared with controls, whereas no significant difference was observed between class IV and class V LN. LC3 signal did not differ significantly between groups, whereas LAMP1 expression and LC3-LAMP1 co-localisation were reduced in LN. In HK-2 cells, crotonylation-deficient MLKL mutants were associated with increased LC3-II and reduced p62, whereas K219Q showed the opposite pattern. Autophagic flux assays using bafilomycin A1 showed that K219R-expressing cells had higher LC3-II levels than WT cells both before and after lysosomal inhibition, with comparable BafA1-induced LC3-II accumulation, consistent with increased autophagosome formation rather than impaired lysosomal degradation. HDAC1 knockdown increased MLKL crotonylation and was accompanied by mTOR activation. MLKL crotonylation enhanced RAB1A guanriphosphat osphate (GTP) binding without altering total RAB1A abundance. RAB1A knockdown in MLKL WT-expressing cells attenuated mTOR phosphorylation and partly reversed the autophagy-suppressive marker profile. Sodium crotonate induced an autophagy-suppressive marker profile that was partly reversed by rapamycin. CONCLUSION: MLKL crotonylation is associated with activation of the RAB1A-mTOR axis and altered tubular autophagy-lysosome pathway homeostasis in LN. These findings suggest that tubular injury-related changes in LN may not be fully reflected by glomerulus-based classification alone.

Humans↗
PubMed2026

Oncolytic HSV-1-Mediated JAG1 Blockade Induces Glioma Senescence-Associated Secretory Phenotype to Increase Macrophage Activation and Cetuximab-Mediated Senolysis.

UNLABELLED: Oncolytic HSV-1 (oHSV) treatment induces Notch signaling and myelosuppression in the tumor microenvironment (TME) of preclinical cancer models. Clinically, the Notch ligand JAG1 was upregulated in patients with recurrent high-grade glioma treated with the oHSV CAN-3110 and correlated with poor prognosis. To better understand endogenous JAG1-mediated signaling in glioma cells and tumor-associated macrophages (TAM), we engineered a JAG1-antagonizing oHSV (OD-0J1) and interrogated its impact on cancer and myeloid cells in the TME. OD-0J1 antagonized JAG1-mediated Notch signaling and suppressed tumor growth in athymic nude and humanized mice, an effect reliant on Notch signaling in tumor cells. Kinome profiling revealed that OD-0J1 treatment suppressed CDK1, resulting in activation of the G2-M cell cycle checkpoint. Cell cycle arrest led to senescence and correlated with increased reactive oxygen species, p62, and autophagosome accumulation and senescence-associated β-galactosidase activity. OD-0J1-induced senescence resulted in increased production of inflammatory chemokines and damage-associated molecular patterns (DAMP), such as IL1β, HMGB1, and extracellular ATP. Coculturing macrophages with OD-0J1-infected tumor cells led to stimulation of chemotactic and proinflammatory pathways, as well as increased Fc receptor activation. Single-cell RNA sequencing and flow cytometric analysis of F4/80+ cells isolated from tumors showed a shift from tumor-supporting TAMs to inflammatory macrophages upon OD-0J1 treatment. Heightened EGFR activation in senescent cells was a mechanism to escape cell death, which created a unique opportunity for cetuximab as a senolytic agent. Combination therapy reduced EGFR signaling and induced macrophage-mediated antibody-dependent cellular cytotoxicity, thereby increasing the antitumor therapeutic efficacy of OD-0J1. SIGNIFICANCE: Leveraging JAG1 antagonism in the context of oncolytic virotherapy rewires macrophage polarization within the tumor microenvironment, which has wide implications for sensitizing tumors to antibodies, senolytic agents, and BiTE therapies.

Humans↗
PubMed1978

Quantitation of ultrastructural changes in mouse pancreatic acinar cells caused by foreign serum.

Quantitative changes in the pancreatic acinar cell organelles were studied in BALB/c mice injected with 1.0 ml fresh rabbit serum intraperitoneally. Groups of 5 mice were killed at 0, 1, 3, 6 and 12 h after the serum injection. Pancreatic tissue was processed for electron microscopy by glutaraldehyde and osmium tetroxide fixation and Epon embedding. The proportions of acinar cell cytoplasm (volume fractions) occupied by zymogen granules, granular endoplasmic reticulum, Golgi apparatus, mitochondria and lysosomes (including autophagosomes) were determined by the point counting method from electron micrographs. The volume fraction of lysosomes increased during the first 3 h and remained markedly elevated up to 12 h. The volume fractions of zymogen granules increased from 12 to 28% in 12 h. It was concluded that the secretory mechanism of pancreatic acinar cells was injured by the foreign serum. The injury caused accumulation of zymogen granules and increased autophagic activity in the acinar cells.

Animals↗
PubMed2026

Transcriptional and histopathological profiling of skeletal muscle in Bla/J mice at the stage of dysferlinopathy manifestation.

Dysferlinopathy is a rare muscular dystrophy characterized by chronic muscle damage and ineffective regeneration. While late-stage morphological changes, such as fibroadipose replacement, are well described, the early molecular mechanisms driving muscle fiber loss and regenerative failure at the onset of the disease remain largely uncharacterized. To address this gap, we investigated the skeletal muscles of dysferlin-deficient Bla/J mice during the early manifestation stage (3 months of age). This exploratory study aimed to identify primary pathomorphogenetic events by correlating the transcriptomic profile of the tissue with its specific histopathological and ultrastructural alterations. We performed a comparative analysis of the m. gastrocnemius in 3-month-old Bla/J mice versus wild-type controls using RNA sequencing, RT-qPCR, histomorphometry and transmission electron microscopy. The results revealed atrophy and muscle fiber necrosis without the expected induction of Fbxo32 and Trim63 ubiquitin ligases, suggesting ubiquitin-proteasome system-independent muscle mass loss. Furthermore, the absence of Casp3, Bak1, and Bad induction, confirmed by the lack of active caspase-3, excluded apoptosis as the primary death mechanism. A differentiation block in satellite cells was confirmed by the lack of Myf5, Myod1, and Myog induction and a trend toward Tead4 suppression, pointing to an early failure of the reparative program. Exploratory RNA sequencing also identified a suppression of Prkn expression accompanied by LC3B-II-positive autophagosome accumulation. Immunohistochemical and immunofluorescent evaluation of the mitochondrial network (TOMM20) revealed abnormal accumulations and dense clumping, indicating impaired organelle clearance. Furthermore, ultrastructural analysis demonstrated internal organelle damage and the presence of myelin-like structures, consistent with a state of stalled mitophagy. Collectively, this exploratory study demonstrates that early muscle atrophy and myofiber necrosis in dysferlinopathy occur independently of canonical ubiquitin-proteasome and apoptotic pathways. Instead, the disease manifestation stage is structurally characterized by stalled mitochondrial clearance and a delayed regenerative response.

Animals↗
PubMed1978

Age-related changes of glomerular basement membrane in normal rats.

The structural changes of the renal glomeruli in development and aging were investigated by electron microscopy in normal rats from 4 to 36 weeks of age at 4 weeks intervals after birth. Infantile rats had an uneven glomerular basement membrane which was characterized by double-layered or mossy appearances of the lamina densa. On the other hand, diffuse and hemispherical thickenings of the basement membrane were observed in older rats. These thickenings were due to the accumulation of basement membrane materials on the epithelial side of the lamina densa. In the older rats, laminae rarae interna and externa were extremely thin. Epithelial cells of the young rat had abundant cytoplasmic organelles and relatively electron-lucent secretory bodies, whereas those of the older rat had less numerous cytoplasmic organelles, many myelinated bodies suggesting autophagosomes, and electron-dense whorl-formed secretory bodies. Mesangial regions of the young rat took small parts of the glomeruli and loosely contacted with endothelial cells. With increasing age, the mesangial matrix also took a greater part of the mesangial regions. The most even figure of the basement membrane was observed in 12 to 16 week old rats.

Aging↗
PubMed2026

Apolipoprotein E promotes papillary thyroid carcinoma progression by activating PINK1/Parkin-mediated mitophagy.

BACKGROUND: Increasing evidence supports a progression-related role of apolipoprotein E (APOE) in papillary thyroid carcinoma (PTC), yet a clear mechanistic explanation for this association is still lacking. Considering the pivotal role of mitochondrial homeostasis in tumorigenesis, the potential role of APOE in promoting PTC progression through mitophagy regulation was investigated. Additionally, the involvement of the PINK1/Parkin-associated pathway in this process was examined to provide insights into its contribution to tumor progression. METHODS: APOE in thyroid carcinoma was characterized in terms of its expression profile, diagnostic relevance, and potential biological functions, based on integrative evidence derived from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. APOE and mitophagy-related protein expression were further examined in PTC tissues by immunohistochemistry. Further evaluation of APOE in PTC cell lines focused on its association with proliferation, apoptosis, and mitophagy, with bidirectional functional perturbation serving as the basis for assessment. Pharmacological inhibitors were used to assess the involvement of mitophagy-related signaling in the observed APOE-dependent phenotypes. Additionally, the in vivo impact of APOE on PTC tumor growth and mitophagy was further investigated through a nude mouse xenograft model, providing insight into its potential role in tumor progression. RESULTS: A significant upregulation of APOE was observed in thyroid carcinoma tissues and PTC cell lines, supporting its potential relevance as a diagnostic biomarker. The modulation of APOE expression significantly influenced PTC cell proliferation and apoptosis, with overexpression promoting cell proliferation and inhibiting apoptosis, while knockdown led to the opposite effects. Mechanistically, APOE overexpression increased AMP-activated protein kinase (AMPK) phosphorylation and decreased mammalian target of rapamycin (mTOR) phosphorylation, accompanied by increased PINK1 and Parkin expression and mitophagy-related changes, including altered mitochondrial membrane potential, reduced overall reactive oxygen species levels, and increased autophagosome formation. Pharmacological inhibition of mitophagy attenuated the proliferative and antiapoptotic effects of APOE. CONCLUSIONS: These findings demonstrate that APOE promotes PTC progression in association with PINK1/Parkin-related mitophagy and modulation of the AMPK/mTOR axis. The APOE-associated mitophagy axis may provide a rationale for future preclinical investigation in PTC.

Apolipoprotein E (APOE)↗
PubMed2024

Membrane-bound O-acyltransferase 7 (MBOAT7) shapes lysosomal lipid homeostasis and function to control alcohol-associated liver injury.

Recent genome-wide association studies (GWAS) have identified a link between single-nucleotide polymorphisms (SNPs) near the MBOAT7 gene and advanced liver diseases. Specifically, the common MBOAT7 variant (rs641738) associated with reduced MBOAT7 expression is implicated in non-alcoholic fatty liver disease (NAFLD), alcohol-associated liver disease (ALD), and liver fibrosis. However, the precise mechanism underlying MBOAT7-driven liver disease progression remains elusive. Previously, we identified MBOAT7-driven acylation of lysophosphatidylinositol lipids as key mechanism suppressing the progression of NAFLD (Gwag et al., 2019). Here, we show that MBOAT7 loss of function promotes ALD via reorganization of lysosomal lipid homeostasis. Circulating levels of MBOAT7 metabolic products are significantly reduced in heavy drinkers compared to healthy controls. Hepatocyte- (Mboat7-HSKO), but not myeloid-specific (Mboat7-MSKO), deletion of Mboat7 exacerbates ethanol-induced liver injury. Lipidomic profiling reveals a reorganization of the hepatic lipidome in Mboat7-HSKO mice, characterized by increased endosomal/lysosomal lipids. Ethanol-exposed Mboat7-HSKO mice exhibit dysregulated autophagic flux and lysosomal biogenesis, associated with impaired transcription factor EB-mediated lysosomal biogenesis and autophagosome accumulation. This study provides mechanistic insights into how MBOAT7 influences ALD progression through dysregulation of lysosomal biogenesis and autophagic flux, highlighting hepatocyte-specific MBOAT7 loss as a key driver of ethanol-induced liver injury.

Animals↗
PubMed1979

Transmission electron microscopy of fetal rat brain cells during neoplastic transformation in cell culture.

Fetal rat brain cells were investigated by transmission electron microscopy during neoplastic transformation in long-term cell culture. Before transfer of the cells to culture, BD IX rat fetuses were treated with a single transplacental pulse of N-ethyl-N-nitrosourea (75 micrograms/g body wt) on the 18th day of gestation. During the early stages (3--4 mo), both glia-like and neuron-like cells were present in the culture, and after 2 months they formed complex aggregates ("nodules"). In contrast, corresponding secondary control cultures consisted of flat, epithelioid neural cells without neuron or astrocyte differentiation. After 3 months, cells with neuron morphology gradually disappeared. Some of the remaining cells contained many autophagosomes. After 5 months, rapid proliferation of rather homogeneous, glia-like populations was accompanied by reduction of microfilament bundles and microtubules, as well as atypical nuclei. Ability to form tumors upon sc implantation into syngeneic hosts was not observed until about 3 months later.

Animals↗
PubMed1979

An ultrastructural study of peritoneal mononuclear phagocytes from Corynebacterium parvum-injected mice.

Peritoneal mononuclear phagocytes harvested from mice 24 h after i.p. injection of C. parvum displayed hypertrophy of the Golgi and smooth endoplasmic reticulum complex with attendant increase in lysosome production. The ingested bacilli were identified within phagolysosomes, within which large myelin figures accumulated. In addition to heterophagic vacuoles, autophagosomes and lipid droplets were observed. These latter two inclusions may reflect a direct or indirect cytopathic effect of C. parvum on the phagocytes.

Animals↗
PubMed1975

A case of halo nevus with effete melanocytes.

Epidermal melanocytes in the depigmenting lesion were examined in one typical case of halo nevus. Vacuolated melanocytes found in the upper layers of epidermis were not, as observed in serial sections, connected to the basal lamina. These melanocytes contained individual as well as aggregated melanosomes in what appeared to be autophagosomes. Part of the cytoplasm of these melanocytes appeared condensed and segregated and their nuclei were often pyknotic. These melanocytes were considered to be degenerated cells which had been detached from the basal layer and were being shed from the skin. Although epidermal keratinocytes, particularly basal cells, were also vacolated. Langerhans cells and non-specific dendritic cells were more or less intact. The total number of these dendritic cells seemed to be increased.

Child↗
PubMed1977

An electron microscopic study of hepatic erythropoiesis in adult mice with Friend virus disease.

A polycythemia-inducing strain of Friend virus was injected into adult mice. Animals were sacrificed on days 2, 5, 9, 11, and 14, and specimens of liver were fixed and embedded for light and electron microscopy. From some mice, samples of bone marrow and spleen were also processed for microscopy. Hepatic erythropoiesis was established as early as 2 to 5 days after inoculation. Often, red cell maturation occurred in typical islands. These included a central macrophage which in many instances appeared to be a Kupffer cell. The number and size of red cell foci increased through day 14. Extensive ineffective erythropoiesis involving erythroblast death occurred within these foci. This premature cell death may be related to large inclusions, thought to be autophagosomes, in the cytoplasm of erythroblasts. A few undifferentiated cells, presumed to be the reticulum cells of Friend virus disease, were observed in the liver at 9 to 14 days after infection. The morphology of these cells resembled that of primitive hemopoietic elements. These studies indicate that the liver, along with the spleen, contributes to the polycythemia in the early phase of Friend virus disease.

Animals↗
PubMed1976

Studies on café au lait spots in neurofibromatosis and pigmented macules of nevus spilus.

Café au lait spots from 14 Japanese patients with neurofibromatosis and nevus spilus from 9 Japanese patients were subjected to the studies on the differences in nature of their melanocytes. When the number of melanocytes of the pigmented lesions was compared with that of the surrounding normal skin, the former was always increased and that of café au lait spot was higher than that of nevus spilus. Giant pigment granules were recognized only in 6 patients out of 14 with neurofibromatosis but not in nevus spilus examined. 2 days after UV irradiation at 4 MED, the number of melanocytes was increased in both surrounding normal skin and pigmented lesion, and the rates of increase were lower in the pigmented lesion. Under the electron microscope, melanocytes in café au lait spots which received an ultraviolet light irradiation showed various changes in their cytoplasm; a development of dendrites containing many mature melanosomes, an increased number of cytoplasmic vacuoles and mitochondria, a development of Golgi apparatus in their cytoplasm, appearances of some dense-bodies and of autophagosomal melanosome-complexes. In nevus spilus, the same kind of changes occurred, but they were moderate compared with those developed in café au lait spots. Melanosomes in the keratinocytes of café au lait spots tended to come together around the nucleus and to form melanosome-complexes; while, melanosomes in the keratinocytes of nevus spilus seemed to be single-dispersed after irradiation. The causative factors of the hyperpigmentation and the different reactivity of melanocytes against UV irradiation in these two pigmented macules were discussed.

Adult↗
PubMed1977

[Morphometric study of the ultrastructure of cells of the zona fasciculata of the adrenals in rats under stress].

A morphometrical study of cell ultrastructures of zona fasciculata of rat adrenal cortex was performed in norm and after immobilization during 4 or 24 hours. A 4 hour's immobilization (alarm reaction) is characterized by adrenocorticocyte activation: relative volumes of mitochondria and reticulum increase by 1.1 and 1.2 times, resp., and lipid volume decrease by 2.6 times. 24 hours after immobilization (the stage of maximal strain), mitochondrion and reticulum volumes decrease by 1.5 and 1.7 times, resp., compared to the initial ones, and autophagosome volumes increase sharply reaching 11% of the cytoplasm volume, i.e. this is the evidence of degeneration clearly registered morphometrically.

Adrenal Cortex↗
PubMed1977

[Studies of transketolase activity in the kidney and the ultrastructure of liver cells of the Rainbow trout (Salmo gairdneri) on an energy rich, thiamine-free diet].

The liver cells of Rainbow trouts (Salmo Gairdneri) were examined with electron-microscopic methods. The animals were fed for 30, 60 or 100 days with a thiaminefree diet. After such a treatment, the mitochondria are swollen in the hepatocytes, the ER often is destroyed and there are large autophagosomes. The effects were the clearer the longer the time of thiaminefree feeding. The activity of transketolase (as an indicator for the supply with thiamine) in the kidney was decreased all the longer the time of thiaminefree feeding. These effects were significant.

Animal Feed↗