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Annexin A5 stimulates autophagy and inhibits endocytosis.

Macroautophagy is a major lysosomal catabolic process activated particularly under starvation in eukaryotic cells. A new organelle, the autophagosome, engulfs cytoplasmic substrates, which are degraded after fusion with endosomes and/or lysosomes. During a shotgun proteome analysis of purified lysosomal membranes from mouse fibroblasts, a Ca(2+)-dependent phospholipid-binding protein, annexin A5, was found to increase on lysosomal membranes under starvation. This suggests a role for this protein, an abundant annexin with a still unknown intracellular function, in starvation-induced lysosomal d…

Autophagy employs a new DAGger against bacteria.

Autophagy can orchestrate innate immune responses to bacterial infection by targeting invading pathogens for lysosomal degradation. In this issue of Cell Host & Microbe, Shahnazari et al. (2010) unveil the role played by the diacylglycerol-PKC pathway in the routing of intracellular Salmonella to autophagy.

Neuronal autophagy in experimental Creutzfeldt-Jakob's disease.

We report an experimental model of Creutzfeldt-Jakob's disease (CJD) in mice leading to the formation of giant autophagic vacuoles (AV) in neurons of the cerebral cortex. These AV appear at the end of the incubation period (4-6 months postinoculation), together with spongy changes and clinical symptoms. Autophagy, a process of intracellular digestion of cell constituents by the lysosomal compartment, is known in many cell types, where it plays a role both in the physiological turnover and in pathological processes and is involved in protein metabolism. The same also occurs in neurons. Here aut…

Protocol for analyzing autophagy-related cellular phenotypes in autophagy-deficient human embryonic stem cell-derived lacrimal gland-like organoids.

Autophagy is a vital catabolic process that maintains cellular homeostasis and survival and supports gland tissue development and function. Here, we present a protocol to characterize the cellular phenotypes of autophagy-deficient (ATG5-/-) lacrimal gland (LG)-like organoids derived from human embryonic stem cells. We describe steps for organoid cryosectioning, followed by the quantitative assessment of cell death and aggresomes using fluorescence-based TUNEL and ProteoStat staining, respectively, along with pharmacological rescue. This approach enables robust evaluation of autophagy-related c…

Down-Regulation of Casein Kinase 1α Contributes to Endometriosis through Phosphatase and Tensin Homolog/Autophagy-Related 7-Mediated Autophagy.

The present study aimed to explore the roles of casein kinase 1α (CK1α) in endometriosis and its underlying mechanisms. Endometrial specimen were collected from the patients and healthy volunteers. The expression patterns of CK1α, phosphatase and tensin homolog (PTEN), and autophagy-related proteins were determined using immunohistochemistry staining, Western blot analysis, and quantitative RT-PCR. Besides, the CK1α-overexpressing cells and PTEN knockdown cells were constructed in the endometrial stromal cells isolated from endometriosis patients. In addition, the cells were transfected with p…

Activation of RARα induces autophagy in SKBR3 breast cancer cells and depletion of key autophagy genes enhances ATRA toxicity.

All-trans retinoic acid (ATRA), a pan-retinoic acid receptor (RAR) agonist, is, along with other retinoids, a promising therapeutic agent for the treatment of a variety of solid tumors. On the one hand, preclinical studies have shown promising anticancer effects of ATRA in breast cancer; on the other hand, resistances occurred. Autophagy is a cellular recycling process that allows the degradation of bulk cellular contents. Tumor cells may take advantage of autophagy to cope with stress caused by anticancer drugs. We therefore wondered if autophagy is activated by ATRA in mammary tumor cells an…

Autophagy Modeles Borrelia burborforferi - производство интерleукина-1β (IL-1β).

Borrelia burdorferi sensu lato является причиной болезни Лайма. Недавние исследования показали, что признание спироше осуществляется при посредничестве TLR2 и NOD2. Последний рецептор связан с введением внутриклеточного процесса разложения, называемого автофагией. В настоящем исследовании впервые показано, что в результате воздействия B. burbdorferi автофагия вводится в действие, и что автофагика модифицирует производство цитокина, зависящего от B. burgdorferi. Концентрационные моноядерные клетки крови человека, обработанные автоматическими ингибиторами, показали увеличение производства IL-1β

Совпадение в аннотации оригинала
Borrelia burgdorferi sensu lato is the causative agent of Lyme disease. Recent studies have shown that recognition of the spirochete is mediated by TLR2 and NOD2. The latter receptor has been associated with the induction of the intracellular degradation process called autophagy. The present study demonstrated for the first time the induction of autophagy by…

Repetitive Compressive Loading Downregulates the Expression of Autophagy-Related Factors, Autophagy Capacity and Cellular Activity in Human Osteoarthritic Chondrocytes.

Mechanical stress is thought to be involved in the pathogenesis and pathophysiology of osteoarthritis (OA). However, much remains to be elucidated regarding how chondrocytes sense and respond to mechanical stress (stress sensing and response factors). Additionally, it still remains unclear whether there are defensive responses and mechanisms to protect against pathological agents and mechanical stress in articular cartilage tissue. This study was designed to determine whether repetitive mechanical force, at physiologic levels, affects the expression of factors regulating autophagy such as the …

UCHL1 alleviates nucleus pulposus cell senescence by promoting chaperone-mediated autophagy antagonizing autophagy-dependent ferroptosis through deubiquitination of HSPA8.

Chaperone-mediated autophagy (CMA), a lysosome-dependent protein degradation pathway, plays a pivotal yet poorly understood role in cellular senescence-related degenerative diseases. Our study sheds light on a novel mechanism whereby UCHL1 plays a crucial role in mitigating nucleus pulposus cell (NPC) senescence and intervertebral disc degeneration (IVDD) by activating CMA to counteract autophagy-dependent ferroptosis. Through sequencing analysis of human samples, we identified UCHL1 as a potential factor influencing disc degeneration. Further research revealed that UCHL1 activates CMA by stab…

The unc-51 like autophagy activating kinase 1-autophagy related 13 complex has distinct functions in tunicamycin-treated cells.

Endoplasmic reticulum (ER) stress and autophagy are regulated by shared signaling pathways, and their dysfunction is directly related to pathological conditions. This study investigated the function of the unc-51 like autophagy activating kinase 1 (ULK1)-autophagy related 13 (ATG13) complex in ER stress conditions through a knockout (KO) approach. Unlike other autophagy genes, KO of ULK1 or ATG13 attenuated ER stress and promoted mammalian target of rapamycin complex 1 (mTORC1) activation. Compared with wild type (WT) cells, ULK1 and ATG13 KO cells displayed increased viability, while beclin 1…

The Role of Autophagy in Long-term Effects of Spinal Cord Injury: Does Exosome Change the Autophagy Process and Vice Versa?

This review explores the synergistic effects of exosomes and autophagy in mitigating spinal cord injury (SCI) while elucidating the underlying molecular mechanisms. We evaluate current literature on the roles of exosomes and autophagy in SCI, highlighting key findings from both in vitro and in vivo studies. Previous research has demonstrated the contributions of these processes to cellular responses under SCI-related conditions. Additionally, animal models have provided insights into the therapeutic potential of modulating exosome and autophagy pathways. The overview discusses the activation o…

Recent Advances in the Roles of Autophagy and Autophagy Proteins in Host Cells During Toxoplasma gondii Infection and Potential Therapeutic Implications.

Toxoplasma gondii is an obligate intracellular protozoan that can cause encephalitis and retinitis in humans. The success of T. gondii as a pathogen depends in part on its ability to form an intracellular niche (parasitophorous vacuole) that allows protection from lysosomal degradation and parasite replication. The parasitophorous vacuole can be targeted by autophagy or by autophagosome-independent processes triggered by autophagy proteins. However, T. gondii has developed many strategies to preserve the integrity of the parasitophorous vacuole. Here, we review the interaction between T. gondi…

A nontoxic concentration of cisplatin induces autophagy in cervical cancer: selective cancer cell death with autophagy inhibition as an adjuvant treatment.

BACKGROUND: Increasing resistance to cisplatin as well as the severity of the adverse effects limit the use of this drug, particularly at high doses. Evidence has implicated the importance of autophagy in cancer resistance as well as the fact that various chemotherapy agents induce autophagy in cancer cells. We therefore aimed to first assess the role of autophagy in cisplatin treatment and second to assess whether a nontoxic concentration of cisplatin, together with autophagy inhibition, is able to maintain its cancer-specific cytotoxic action. METHODS: Three human cervical cell lines were u…

Repopulation of autophagy-deficient stromal cells with autophagy-intact cells after repeated breeding in uterine mesenchyme-specific Atg7 knockout mice.

OBJECTIVE: Autophagy is highly active in ovariectomized mice experiencing hormone deprivation, especially in the uterine mesenchyme. Autophagy is responsible for the turnover of vasoactive factors in the uterus, which was demonstrated in anti-Müllerian hormone receptor type 2 receptor (Amhr2)-Cre-driven autophagy-related gene 7 (Atg7) knockout (Amhr-Cre/Atg7f/f mice). In that study, we uncovered a striking difference in the amount of sequestosome 1 (SQSTM1) accumulation between virgin mice and breeder mice with the same genotype. Herein, we aimed to determine whether repeated breeding changed …

Autophagy Defects and Mitochondrial Retention in Erythroid Diseases.

Erythropoiesis requires extensive cellular remodeling, culminating in enucleation and organelle clearance to generate mature red blood cells (RBCs). Over the past 15 years, accumulating evidence has established that macroautophagy-particularly ULK1-, NIX-, and PINK1-dependent mitophagy-plays a central role in erythroid maturation. Defective autophagy can lead to mitochondrial retention, increased reactive oxygen species (ROS) production, membrane alterations, and ineffective erythropoiesis. Such abnormalities have now been documented in several hematological disorders, including myelodysplasti…

Neuroinflammation, Autophagy, and Neurodegeneration: Mechanisms and Therapeutic Insights.

Neuroinflammation and autophagy dysregulation are critical in the pathogenesis of neurodegenerative diseases like Alzheimer's, Parkinson's, and Huntington's disease. Neuroinflammation occurs after a sustained immune response, which transitions into a chronic pathological state, leading to the sustained generation of pro-inflammatory cytokines and oxidative stress, causing neuronal damage. Meanwhile, defective autophagy exacerbates disease by promoting protein accumulation, e.g., amyloid-β, tau, and α-synuclein, thereby enhancing neuroinflammation. In this review, we focus on critical pathways,…

A novel mechanism of autophagy-dependent immunosuppression in cancer?

Autophagy underlies several immunosuppressive mechanisms that collectively endow cancer cells with prominent immunoevasive features. Recent data from Hoslett et al. demonstrate that a specialized variant of autophagy commonly known as nucleophagy actively removes PARP1 molecules trapped on DNA upon pharmacological inhibition, mediating robust cytoprotective and possibly immunosuppressive effects.

SNAP23 regulates CPEB4 in the autophagy of hepatocellular carcinoma.

SNAP23 and CPEB4 exhibit promising potential in hepatocellular carcinoma (HCC). This study aimed to investigate their roles in HCC progression and the underlying molecular mechanisms. Using bioinformatics analysis and in vitro experiments in Huh7 cells, we found that SNAP23 was upregulated in HCC and positively correlated with CPEB4. Silencing either gene significantly suppressed cell proliferation and migration while inducing apoptosis. Mechanistically, SNAP23 acted upstream of CPEB4 to regulate autophagy and oxidative stress. Knockdown of SNAP23 or CPEB4 impaired autophagic flux and reduced …

[Regulation of Mitochondrial Autophagy by FADD in Jurkat Cells].

OBJECTIVE: To investigate the regulatory effect of Fas-associated death domain protein (FADD) on the number of mitochondria in Jurkat cells. METHODS: The FADD gene in Jurkat cell line was knocked out by lentivirus packaging CRISPR/Cas9-FADD plasmid. The protein levels of FADD and PGC1-α in virus-transfected Jurkat cells and the expression of LC3B/β-actin protein after rapamycin-induced autophagy were detected by Western blot. And the effect of FADD on autophagy was reversely validated through a rescue experiment. qPCR was used for relative quantification of mtCO1/β-globin in rapamycin induced…

Reconstitution of multistep recruitment of ULK1 to membranes in autophagy.

The human Unc51-like kinase 1 (ULK1) autophagy-initiating complex consists of ULK1, FIP200, and the Hop/Rev7/Mad2 (HORMA) domain heterodimer ATG13:ATG101. Phosphatidylinositol 3-phosphate (PI3P) is essential to recruit ULK1 complex (ULK1C) to membranes for ULK1, but ULK1C subunits do not contain PI3P-binding domains. Here, we show that the ATG13:ATG101 dimer forms a complex with the PI3P-binding protein WD40 interacting with phosphoinositide protein 3 (WIPI3), as well as WIPI2. Bound to WIPI2 and WIPI3, ATG13:ATG101 inserts its Trp-Phe (WF) finger into the membrane. Molecular dynamics simulati…