Search results for "Autophagosome"
showing 10 items of 26 documents
The role of the co-chaperone BAG3 in selective macroautophagy: implications for aging and disease
2012
Maintenance of protein homeostasis, correct protein folding, refolding and clearance is of central importance for the function and survival of every cell. Here, the degradation of proteins is of particular importance, especially during aging and certain degenerative disorders when the protein load is increased. During cellular aging as well as under acute stress, there is a reciprocal change in expression of two members of the BAG (Bcl-2-associated athanogene) family, BAG1 and BAG3. While BAG1 serves an important function during the degradation of ubiquitinated proteins via the proteasome, BAG3 is the mediator of a novel macroautophagy pathway. This BAG3-mediated macroautophagy is based on …
Artesunate Activates Mitochondrial Apoptosis in Breast Cancer Cells via Iron-catalyzed Lysosomal Reactive Oxygen Species Production
2011
The antimalarial agent artesunate (ART) activates programmed cell death (PCD) in cancer cells in a manner dependent on the presence of iron and the generation of reactive oxygen species. In malaria parasites, ART cytotoxicity originates from interactions with heme-derived iron within the food vacuole. The analogous digestive compartment of mammalian cells, the lysosome, similarly contains high levels of redox-active iron and in response to specific stimuli can initiate mitochondrial apoptosis. We thus investigated the role of lysosomes in ART-induced PCD and determined that in MCF-7 breast cancer cells ART activates lysosome-dependent mitochondrial outer membrane permeabilization. ART impac…
p62: Friend or Foe? Evidences for OncoJanus and NeuroJanus Roles
2020
p62 is a versatile protein involved in the delicate balance between cell death and survival, which is fundamental for cell fate decision in the context of both cancer and neurodegenerative diseases. As an autophagy adaptor, p62 recognizes polyubiquitin chains and interacts with LC3, thereby targeting the selected cargo to the autophagosome with consequent autophagic degradation. Beside this function, p62 behaves as an interactive hub in multiple signalling including those mediated by Nrf2, NF-κB, caspase-8, and mTORC1. The protein is thus crucial for the control of oxidative stress, inflammation and cell survival, apoptosis, and metabolic reprogramming, respectively. As a multifunctional pr…
Autophagy in development and stress responses of plants.
2006
The uptake and degradation of cytoplasmic material by vacuolar autophagy in plants has been studied extensively by electron microscopy and shown to be involved in developmental processes such as vacuole formation, deposition of seed storage proteins and senescence, and in the response of plants to nutrient starvation and to pathogens. The isolation of genes required for autophagy in yeast has allowed the identification of many of the corresponding Arabidopsis genes based on sequence similarity. Knockout mutations in some of these Arabidopsis genes have revealed physiological roles for autophagy in nutrient recycling during nitrogen deficiency and in senescence. Recently, markers for monitor…
Starvation-induced expression of autophagy-related genes in Arabidopsis
2005
Background information. Autophagy is a catabolic process for degradation of cytoplasmic components in the vacuolar apparatus. A genome-wide survey recently showed evolutionary conservation among autophagy genes in yeast, mammals and plants. To elucidate the molecular and subcellular machinery responsible for the sequestration and subsequent digestion of intracellular material in plants, we utilized a combination of morphological and molecular methods (confocal laser-scanning microscopy, transmission electron microscopy and real-time PCR respectively). Results. Autophagy in Arabidopsis thaliana suspension-cultured cells was induced by carbon starvation, which triggered an immediate arrest of…
Involvement of PAR-4 in Cannabinoid-Dependent Sensitization of Osteosarcoma Cells to TRAIL-Induced Apoptosis
2014
The synthetic cannabinoid WIN 55,212-2 is a potent cannabinoid receptor agonist with anticancer potential. Experiments were performed to determine the effects of WIN on proliferation, cell cycle distribution, and programmed cell death in human osteosarcoma MG63 and Saos-2 cells. Results show that WIN induced G2/M cell cycle arrest, which was associated with the induction of the main markers of ER stress (GRP78, CHOP and TRB3). In treated cells we also observed the conversion of the cytosolic form of the autophagosome marker LC3-I into LC3-II (the lipidated form located on the autophagosome membrane) and the enhanced incorporation of monodansylcadaverine and acridine orange, two markers of t…
Sprint and Strength Training Modulates Autophagy and Proteostasis in Aging Sprinters
2020
Purpose Exercise and aging may modulate muscle protein homeostasis and autophagy, but few studies examine highly-trained middle-aged or older individuals. This study elucidated the effects of a new long-term training stimulus on markers of muscle autophagy and unfolded protein response (UPR) and on sprint running performance in masters sprinters. Methods Thirty-two male competitive sprinters (aged 40–76 years) were randomly divided into experimental (EX) and control (CTRL) groups. The EX training program was a combination of heavy and explosive strength and sprint exercises aimed at improving sprint performance. Fifteen and thirteen participants completed the 20-week intervention period in …
Lung autophagic response following exposure of mice to whole body irradiation, with and without amifostine
2010
Research highlights: {yields} We investigated the effect 6 Gy of WBI on the autophagic machinery of normal mouse lung. {yields} Irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. {yields} The membrane bound LC3A-II protein levels increased in the cytosolic fraction (not in the pellet), contrasting the patterns noted after starvation-induced autophagy. {yields} Administration of amifostine, reversed all the LC3A and p62 findings, suggesting protection of the normal autophagic function. -- Abstract: Purpose: The effect of ionizing irradiation on the autop…
De Novo prion aggregates trigger autophagy in skeletal muscle
2014
ABSTRACT In certain sporadic, familial, and infectious prion diseases, the prion protein misfolds and aggregates in skeletal muscle in addition to the brain and spinal cord. In myocytes, prion aggregates accumulate intracellularly, yet little is known about clearance pathways. Here we investigated the clearance of prion aggregates in muscle of transgenic mice that develop prion disease de novo . In addition to neurodegeneration, aged mice developed a degenerative myopathy, with scattered myocytes containing ubiquitinated, intracellular prion inclusions that were adjacent to myocytes lacking inclusions. Myocytes also showed elevated levels of the endoplasmic reticulum chaperone Grp78/BiP, su…
Protein content and lipid profiling of isolated native autophagosomes
2021
AbstractAutophagy is a central eukaryotic catabolic pathway responsible for clearance and recycling of an extensive portfolio of cargoes, which are packed in vesicles, called autophagosomes, and are delivered to lysosomes for degradation. Besides basal autophagy, which constantly degrades cellular material, the pathway is highly responsive to several stress conditions. However, the exact protein content and phospholipid composition of autophagosomes under changing autophagy conditions remain elusive so far. Here, we introduce a FACS-based approach for isolation of native unmanipulated autophagosomes and ensure the quality of the preparations. Employing quantitative proteomics and phospholip…