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There are 113 results for Autophagy (displaying 41 to 50).

Atg1‐mediated myosin II activation regulates autophagosome formation during starvation‐induced autophagy

Autophagy is a membrane‐mediated degradation process of macromolecule recycling. Although the formation of double‐membrane degradation vesicles (autophagosomes) is known to have a central role in autophagy, the mechanism underlying this process remains elusive. The serine/threonine kinase Atg1 has a key role in the induction of autophagy. In this study, we show that overexpression of Drosophila Atg1 promotes the phosphorylation‐dependent activation of the actin‐associated motor protein myosin …

Involvement of zipper‐interacting protein kinase (ZIPK) and myosin II in starvation‐induced autophagy. (A) MCF7/GFP–LC3 cells stably infected with lentivirus expressing control (shLuc), ZIPK, or non‐muscle myosin heavy chain‐IIA (NMHC‐IIA) shRNA were cultured in nutrient‐rich medium (DMEM) or starvation medium (Earle's balanced salt solution; EBSS) in the presence or absence of lysosomal inhibitor bafilomycin A1 (BafA1) for 2 h. Depletion of ZIPK and NMHC‐IIA markedly inhibited starvation …

Atg1–spaghetti‐squash activator (Sqa)‐mediated myosin II activation is required for starvation‐induced autophagy. (A, B) Activation of myosin II on nutrient deprivation. The larval fat body of denoted genotypes under fed or starved conditions were dissected, lysed, and subjected to western blot analysis using antibodies specific for phospho‐myosin regulatory light chain (MRLC) and total MRLC. The Rheb, SqaRNAi, Sqa‐T279A, spaghetti‐squash (SqhA20A21), and Atg7RNAi transgenes were expressed …

Autophagy is a highly conserved catabolic process in which long‐lived proteins, RNA, and organelles are degraded in lysosomes. It occurs at a relatively low level during normal growth conditions but can be strongly induced under such environmental stress as nutrient starvation, hypoxia, and oxidative stress. Once autophagy is induced, cytoplasmic components are engulfed within specialized double‐membrane vesicles known as autophagosomes ( ). These vesicles subsequently fuse with lysosomes …

Hong‐Wen Tang et al. The EMBO Journal February 2011

Recruitment of TBK1 to cytosol‐invading Salmonella induces WIPI2‐dependent antibacterial autophagy

Mammalian cells deploy autophagy to defend their cytosol against bacterial invaders. Anti‐bacterial autophagy relies on the core autophagy machinery, cargo receptors, and “eat‐me” signals such as galectin‐8 and ubiquitin that label bacteria as autophagy cargo. Anti‐bacterial autophagy also requires the kinase TBK 1, whose role in autophagy has remained enigmatic. Here we show that recruitment of WIPI2, itself essential for anti‐bacterial autophagy, is dependent on the localization …

… Anti‐bacterial autophagy provides potent cell‐autonomous immunity against bacterial attempts to colonize the cytosol of mammalian cells (Kuballa et al , ; Deretic et al , ; Randow et al , ). The defense of the gut epithelium against bacteria in particular is crucially dependent on anti‐bacterial autophagy, since mice lacking the essential autophagy gene Atg5 in enterocytes suffer from tissue invasion by commensal bacteria and from increased pathology upon infection with Salmonella enterica …

Teresa LM Thurston et al. The EMBO Journal August 2016

Genome‐wide screen identifies signaling pathways that regulate autophagy during Caenorhabditis elegans development

The mechanisms that coordinate the regulation of autophagy with developmental signaling during multicellular organism development remain largely unknown. Here, we show that impaired function of ribosomal protein RPL ‐43 causes an accumulation of SQST ‐1 aggregates in the larval intestine, which are removed upon autophagy induction. Using this model to screen for autophagy regulators, we identify 139 genes that promote autophagy activity upon inactivation. Various signaling pathways, including …

Autophagy is an evolutionarily conserved lysosome‐mediated degradation process. It involves the formation of a cup‐shaped membrane sac, known as the isolation membrane, which expands and seals to form an enclosed double‐membrane autophagosome. In higher eukaryotes, autophagosomes mature by fusing with endosomes before fusing with lysosomes to form degradative autolysosomes . Distinct steps of autophagosome formation require different sets of genes . The Atg1/Atg13 kinase complex and the Vps34 …

Bin Guo et al. EMBO Reports June 2014

Lysosome membrane lipid microdomains: novel regulators of chaperone‐mediated autophagy

Chaperone‐mediated autophagy (CMA) is a selective mechanism for the degradation of soluble cytosolic proteins in lysosomes. The limiting step of this type of autophagy is the binding of substrates to the lysosome‐associated membrane protein type 2A (LAMP‐2A). In this work, we identify a dynamic subcompartmentalization of LAMP‐2A in the lysosomal membrane, which underlies the molecular basis for the regulation of LAMP‐2A function in CMA. A percentage of LAMP‐2A localizes in discrete lysosomal …

… A subset of cytosolic proteins, which contain in their amino‐acid sequence a pentapeptide motif biochemically related to KFERQ, can be selectively degraded by lysosomes via chaperone‐mediated autophagy (CMA) (reviewed in ). The CMA‐targeting motif is first recognized by a cytosolic chaperone (the heat shock cognate protein of 70 kDa or hsc70) and its co‐chaperones. This complex is then targeted to the lysosomal membrane, where the substrate binds to the lysosome‐associated membrane protein type …

Susmita Kaushik et al. The EMBO Journal September 2006

Cathepsin A regulates chaperone‐mediated autophagy through cleavage of the lysosomal receptor

Protective protein/cathepsin A (PPCA) has a serine carboxypeptidase activity of unknown physiological function. We now demonstrate that this protease activity triggers the degradation of the lysosome‐associated membrane protein type 2a (lamp2a), a receptor for chaperone‐mediated autophagy (CMA). Degrada tion of lamp2a is important because its level in the lysosomal membrane is a rate‐limiting step of CMA. Cells defective in PPCA show reduced rates of lamp2a degradation, higher levels of lamp2a …

… protein type 2a (lamp2a), a receptor for chaperone‐mediated autophagy (CMA). The amount of receptor at the lyso somal membrane is a rate‐limiting step in CMA ( ), so lamp2a cleavage regulates the activity of this lysosomal pathway of protein degradation. Approximately 30% of cytosolic proteins can be selectively degraded in lysosomes by CMA ( ; ). Substrate proteins contain in their sequence a targeting motif, biochemically related to the pentapeptide KFERQ, which is recognized by a cytosolic …

Ana Maria Cuervo et al. The EMBO Journal January 2003

Autophagy proteins control goblet cell function by potentiating reactive oxygen species production

Delivery of granule contents to epithelial surfaces by secretory cells is a critical physiologic process. In the intestine, goblet cells secrete mucus that is required for homeostasis. Autophagy proteins are required for secretion in some cases, though the mechanism and cell biological basis for this requirement remain unknown. We found that in colonic goblet cells, proteins involved in initiation and elongation of autophagosomes were required for efficient mucus secretion. The autophagy

… or diminished secretion ( ; ). Loss of autophagy proteins leads to defects in the function of various secretory cell types, though the precise mechanism is unclear ( ; ; ; ; ; ). Specifically in the intestine, autophagy proteins are of interest as multiple proteins in this pathway have been identified in genome‐wide association studies for inflammatory bowel disease ( ; ). Autophagy (macroautophagy) is a bulk degradation process in which a curving membrane cistern (a phagophore) encloses cytoplasm …

Khushbu K Patel et al. The EMBO Journal December 2013

DAP‐kinase‐mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl‐XL and induction of autophagy

Autophagy, an evolutionarily conserved process, has functions both in cytoprotective and programmed cell death mechanisms. Beclin 1, an essential autophagic protein, was recently identified as a BH3‐domain‐only protein that binds to Bcl‐2 anti‐apoptotic family members. The dissociation of beclin 1 from its Bcl‐2 inhibitors is essential for its autophagic activity, and therefore should be tightly controlled. Here, we show that death‐associated protein kinase (DAPK) regulates this process …

Autophagy is an evolutionarily conserved process that is characterized by the formation of double‐membrane‐enclosed autophagosomes that engulf intracellular organelles and cytoplasmic constituents, and deliver them to the lysosomes for degradation. In addition to its cytoprotective functions in stressed cells ( ), autophagy can also act as a cell death mechanism under some conditions ( ; ; ; ). Beclin 1, a haplo‐insufficient tumour suppressor that was initially identified as a Bcl‐2‐binding …

Einat Zalckvar et al. EMBO Reports February 2009

Impairment of chaperone‐mediated autophagy leads to selective lysosomal degradation defects in the lysosomal storage disease cystinosis

Metabolite accumulation in lysosomal storage disorders ( LSD s) results in impaired cell function and multi‐systemic disease. Although substrate reduction and lysosomal overload‐decreasing therapies can ameliorate disease progression, the significance of lysosomal overload‐independent mechanisms in the development of cellular dysfunction is unknown for most LSD s. Here, we identify a mechanism of impaired chaperone‐mediated autophagy ( CMA ) in cystinosis, a LSD caused by defects in the cystine …

… is missing. Autophagy is an essential cellular process that consists of the digestion of cytoplasmic components through lysosomal degradation (Klionsky, ). Autophagic pathways represent a major protective mechanism that, in addition to their role in providing cells with amino acids and nutrients, also allow cell survival in response to multiple stressors, including starvation and oxidative stress, and help defend organisms against degenerative and neoplastic diseases (Levine & Kroemer, ; Martinou …

Gennaro Napolitano et al. EMBO molecular medicine February 2015

The structure of Atg4B–LC3 complex reveals the mechanism of LC3 processing and delipidation during autophagy

Atg8 is conjugated to phosphatidylethanolamine (PE) by ubiquitin‐like conjugation reactions. Atg8 has at least two functions in autophagy: membrane biogenesis and target recognition. Regulation of PE conjugation and deconjugation of Atg8 is crucial for these functions in which Atg4 has a critical function by both processing Atg8 precursors and deconjugating Atg8–PE. Here, we report the crystal structures of catalytically inert human Atg4B (HsAtg4B) in complex with processed and unprocessed …

Autophagy is the process through which the bulk degradation of cytoplasmic components by the lysosomal/vacuolar system occurs ( ), and it has a critical function in numerous biological processes ( ). In autophagy, a double‐membrane structure called an autophagosome sequesters a portion of the cytoplasm and fuses with the lysosome/vacuole to deliver its contents into the organelle lumen ( ). Genetic approaches in Saccharomyces cerevisiae have identified many autophagy‐related ( ATG ) genes …

Kenji Satoo et al. The EMBO Journal May 2009

Two newly identified sites in the ubiquitin‐like protein Atg8 are essential for autophagy

Atg8, a member of a novel ubiquitin‐like protein family, is an essential component of the autophagic machinery in yeast. This protein undergoes reversible conjugation to phosphatidylethanolamine through a multistep process in which cleavage of Atg8 by a specific protease is followed by ubiquitin‐like conjugation processes. Here, we identify two essential sites in Atg8, one of them involving residues Phe 77 and Phe 79 and the other, located on the opposite surface of Atg8, residues Tyr 49 and Leu 50. We show that these two sites are associated with different functions of Atg8: Phe 77 and Phe 79 seem to be part of the recognition site for Atg4, a cystein protease that acts also as a deubiquitination enzyme, whereas Tyr 49 and Leu 50 act downstream of the lipidation step. These two newly identified distinct sites that are essential for Atg8 activity provide an explanation for the many protein–protein interactions of this low‐molecular‐weight protein.

… The autophagic pathway mediates delivery of cytosolic proteins and organelles for degradation within the lysosomes/vacuole compartments. Recent studies linked autophagy with numerous physiological conditions, including liver diseases, muscular disorders, neurodegeneration, pathogen infections and cancer ( ; ). Genetic screens in the yeast Saccharomyces cerevisiae identified 16 autophagy‐related genes ( ATG s) that are essential for this process ( ). This group of genes includes two unique …

Nira Amar et al. EMBO Reports May 2006
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