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https://www.readbyqxmd.com/read/28340346/the-upsides-and-downsides-of-organelle-interconnectivity
#1
REVIEW
Daniel E Gottschling, Thomas Nyström
Interconnectivity and feedback control are hallmarks of biological systems. This includes communication between organelles, which allows them to function and adapt to changing cellular environments. While the specific mechanisms for all communications remain opaque, unraveling the wiring of organelle networks is critical to understand how biological systems are built and why they might collapse, as occurs in aging. A comprehensive understanding of all the routes involved in inter-organelle communication is still lacking, but important themes are beginning to emerge, primarily in budding yeast...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28338655/evolution-of-caspase-mediated-cell-death-and-differentiation-twins-separated-at-birth
#2
REVIEW
Ryan A V Bell, Lynn A Megeney
The phenotypic and biochemical similarities between caspase-mediated apoptosis and cellular differentiation are striking. They include such diverse phenomenon as mitochondrial membrane perturbations, cytoskeletal rearrangements and DNA fragmentation. The parallels between the two disparate processes suggest some common ancestry and highlight the paradoxical nature of the death-centric view of caspases. That is, what is the driving selective pressure that sustains death-inducing proteins throughout eukaryotic evolution? Plausibly, caspase function may be rooted in a primordial non-death function, such as cell differentiation, and was co-opted for its role in programmed cell death...
March 24, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28337642/the-small-heat-shock-proteins-%C3%AE-b-crystallin-hspb5-and-hsp27-hspb1-inhibit-the-intracellular-aggregation-of-%C3%AE-synuclein
#3
Dezerae Cox, Heath Ecroyd
Protein homeostasis, or proteostasis, is the process of maintaining the conformational and functional integrity of the proteome. Proteostasis is preserved in the face of stress by a complex network of cellular machinery, including the small heat shock molecular chaperone proteins (sHsps), which act to inhibit the aggregation and deposition of misfolded protein intermediates. Despite this, the pathogenesis of several neurodegenerative diseases has been inextricably linked with the amyloid fibrillar aggregation and deposition of α-synuclein (α-syn)...
March 23, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28334862/the-wilms-tumor-protein-wt1-contributes-to-female-fertility-by-regulating-oviductal-proteostasis
#4
Abinaya Nathan, Peter Reinhardt, Dagmar Kruspe, Tjard Jörß, Marco Groth, Hendrik Nolte, Andreas Habenicht, Jörg Herrmann, Verena Holschbach, Bettina Toth, Marcus Krüger, Zhao-Qi Wang, Matthias Platzer, Christoph Englert
Although the zinc finger transcription factor Wt1 has been linked to female fertility, its precise role in this process has not yet been understood. We have sequenced the WT1 exons in a panel of patients with idiopathic infertility and have identified a missense mutation in WT1 in one patient out of eight. This mutation leads to an amino acid change within the zinc finger domain and results in reduced DNA binding. We utilized Wt1+/- mice as a model to mechanistically pinpoint the consequences of reduced Wt1 levels for female fertility...
March 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334762/missense-uros-mutations-causing-congenital-erythropoietic-porphyria-reduce-uros-homeostasis-that-can-be-rescued-by-proteasome-inhibition
#5
Jean-Marc Blouin, Ganeko Bernardo-Seisdedos, Emma Sasso, Julie Esteve, Cécile Ged, Magalie Lalanne, Arantza Sanz-Parra, Pedro Urquiza, Hubert de Verneuil, Oscar Millet, Emmanuel Richard
Congenital erythropoietic porphyria (CEP) is an inborn error of heme biosynthesis characterized by uroporphyrinogen III synthase (UROS) deficiency resulting in deleterious porphyrin accumulation in blood cells responsible for hemolytic anemia and cutaneous photosensitivity. We analyzed here the molecular basis of UROS impairment associated with twenty nine UROS missense mutations actually described in CEP patients. Using a computational and biophysical joint approach we predicted that most disease-causing mutations would affect UROS folding and stability...
February 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334751/atp13a2-park9-regulates-endo-lysosomal-cargo-sorting-and-proteostasis-through-a-novel-pi-3-5-p2-mediated-scaffolding-function
#6
S Demirsoy, S Martin, S Motamedi, S van Veen, T Holemans, C Van den Haute, A Jordanova, V Baekelandt, P Vangheluwe, P Agostinis
ATP13A2 (also called PARK9), is a transmembrane endo-/lysosomal-associated P5 type transport ATPase. Loss-of-function mutations in ATP13A2 result in the Kufor-Rakeb Syndrome (KRS), a form of autosomal Parkinson's disease (PD). In spite of a growing interest in ATP13A2, very little is known about its physiological role in stressed cells. Recent studies suggest that the N-terminal domain of ATP13A2 may hold key regulatory functions, but their nature remains incompletely understood. To this end, we generated a set of melanoma and neuroblastoma cell lines stably overexpressing wild-type (WT), catalytically inactive (D508N) and N-terminal mutants, or shRNA against ATP13A2...
February 22, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28333578/hormetic-heat-shock-and-hsf-1-overexpression-improve-c-elegans-survival-by-inducing-autophagy
#7
Caroline Kumsta, Malene Hansen
The cellular recycling process of macroautophagy/autophagy is an essential homeostatic system induced by various stresses, but it remains unclear how autophagy contributes to organismal stress resistance. In a recent study, we report that a mild and physiologically beneficial ("hormetic") heat shock as well as overexpression of the heat-shock responsive transcription factor HSF-1 systemically increases autophagy in C. elegans. Accordingly, we found HSF-1- and heat stress-inducible autophagy to be required for C...
March 23, 2017: Autophagy
https://www.readbyqxmd.com/read/28332488/parkinson-disease
#8
REVIEW
Werner Poewe, Klaus Seppi, Caroline M Tanner, Glenda M Halliday, Patrik Brundin, Jens Volkmann, Anette-Eleonore Schrag, Anthony E Lang
Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability...
March 23, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28315482/modes-of-antibacterial-action-of-curcumin-under-dark-and-light-conditions-a-toxicoproteomics-approach
#9
Ilya Shlar, Samir Droby, Victor Rodov
Curcumin is a potent natural food-grade antimicrobial compound. Exposure to light further enhances its antimicrobial capacity. Proteomic methods were used in this study for investigating the mechanistic aspects of the antibacterial curcumin effects in the dark and upon illumination. Escherichia coli cells exposed to water-dispersible curcumin-methyl-β-cyclodextrin inclusion complex under dark and light conditions were compared with the non-treated cells kept under the same illumination regimes. Curcumin treatment in the dark evoked adaptive responses aimed at mitigation of oxidative stress, DNA protection, proteostasis, modulation of redox state via changing NADH level, and gasotransmitter (H2S and NH3) biosynthesis...
March 14, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28315241/silpronaq-a-convenient-approach-for-proteome-wide-analysis-of-protein-n-termini-and-n-terminal-acetylation-quantitation
#10
Willy V Bienvenut, Carmela Giglione, Thierry Meinnel
Protein N-terminal modifications have recently been involved in overall proteostasis through their impact on cell fate and protein life time. This explains the development of new approaches to characterize more precisely the N-terminal end of mature proteins. Although few approaches are available to perform N-terminal enrichment based on positive or negative discriminations, these methods are usually restricted to the enrichment in N-terminal peptides and their characterization by mass spectrometry. Recent investigation highlights both (1) the knowledge of the N-terminal acetylation status of most cytosolic proteins and (2) post-translational addition of this modification on the N-terminus of nuclear coded chloroplast proteins imported in the plastid and after the cleavage of the transit peptide...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28314264/targeting-the-unfolded-protein-response-as-a-potential-therapeutic-strategy-in-renal-carcinoma-cells-exposed-to-cyclosporine-a
#11
Sandra Bodeau, Chloé Sauzay, Rémy Nyga, Christophe Louandre, Véronique Descamps, Catherine François, Corinne Godin, Gabriel Choukroun, Antoine Galmiche
BACKGROUND/AIM: Organ transplant patients treated with the immunosuppressive drug cyclosporine A often present malignant kidney tumors. Cyclosporine A can promote oncogenesis in a cell-intrinsic manner by increasing the production of vascular endothelial growth factor (VEGF). MATERIALS AND METHODS: We explored the impact of cyclosporine A and the role of the unfolded protein response (UPR) on three human renal cell carcinoma (RCC) cell lines under normoxic and hypoxic (1% O2) conditions...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28300624/neurotoxicity-of-the-steroidal-alkaloids-tomatine-and-tomatidine-is-rip1-kinase-and-caspase-independent-and-involves-the-eif2%C3%AE-branch-of-the-endoplasmic-reticulum
#12
Daniela Correia da Silva, Paula B Andrade, Patrícia Valentão, David M Pereira
Steroidal alkaloids are a class of natural products that occur in several species of the Solanaceae family. In the case of tomato plant (Lycopersicon esculentum Mill.), tomatine and its aglycone, tomatidine, are the most representative molecules. These steroidal alkaloids have already shown several potentially useful biological activities, from anticancer to anti-inflammatory or antibacterial. In this work, the toxicity of these molecules in neuronal cells, namely in the neuroblastoma cell line SH-SY5Y, was assessed, emphasis being given to the cellular mechanisms underlying the effects observed...
March 11, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28298488/the-ribosome-bound-quality-control-complex-remains-associated-to-aberrant-peptides-during-their-proteasomal-targeting-and-interacts-with-tom1-to-limit-protein-aggregation
#13
Quentin Defenouillère, Abdelkader Namane, John Mouaikel, Alain Jacquier, Micheline Fromont-Racine
Protein quality control mechanisms eliminate defective polypeptides to ensure proteostasis and to avoid the toxicity of protein aggregates. In eukaryotes, the Ribosome-bound Quality Control (RQC) complex detects aberrant nascent peptides that remain stalled in 60S ribosomal particles due to a dysfunction in translation termination. The RQC complex polyubiquitylates aberrant polypeptides and recruits a Cdc48 hexamer to extract them from 60S particles in order to escort them to the proteasome for degradation...
March 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28296976/exome-wide-association-study-reveals-novel-susceptibility-genes-to-sporadic-dilated-cardiomyopathy
#14
Ulrike Esslinger, Sophie Garnier, Agathe Korniat, Carole Proust, Georgios Kararigas, Martina Müller-Nurasyid, Jean-Philippe Empana, Michael P Morley, Claire Perret, Klaus Stark, Alexander G Bick, Sanjay K Prasad, Jennifer Kriebel, Jin Li, Laurence Tiret, Konstantin Strauch, Declan P O'Regan, Kenneth B Marguiles, Jonathan G Seidman, Pierre Boutouyrie, Patrick Lacolley, Xavier Jouven, Christian Hengstenberg, Michel Komajda, Hakon Hakonarson, Richard Isnard, Eloisa Arbustini, Harald Grallert, Stuart A Cook, Christine E Seidman, Vera Regitz-Zagrosek, Thomas P Cappola, Philippe Charron, François Cambien, Eric Villard
AIMS: Dilated cardiomyopathy (DCM) is an important cause of heart failure with a strong familial component. We performed an exome-wide array-based association study (EWAS) to assess the contribution of missense variants to sporadic DCM. METHODS AND RESULTS: 116,855 single nucleotide variants (SNVs) were analyzed in 2796 DCM patients and 6877 control subjects from 6 populations of European ancestry. We confirmed two previously identified associations with SNVs in BAG3 and ZBTB17 and discovered six novel DCM-associated loci (Q-value<0...
2017: PloS One
https://www.readbyqxmd.com/read/28295473/mtorc1-senses-stresses-coupling-stress-to-proteostasis
#15
REVIEW
Kuo-Hui Su, Chengkai Dai
Beyond protein synthesis and autophagy, emerging evidence has implicated mTORC1 in regulating protein folding and proteasomal degradation as well, highlighting its prominent role in cellular proteome homeostasis or proteostasis. In addition to growth signals, mTORC1 senses and responds to a wide array of stresses, including energetic/metabolic stress, genotoxic stress, oxidative stress, osmotic stress, ER stress, proteotoxic stress, and psychological stress. Whereas growth signals unanimously stimulate mTORC1, stresses exert complex impacts on mTORC1, most of which are repressive...
March 15, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28295407/alcoholic-liver-disease-on-the-rise-interorgan-cross-talk-driving-liver-injury
#16
Srinivasan Dasarathy, J Mark Brown
Advanced alcoholic liver disease (ALD) represents a substantial public health burden, threatening the lives of more than ten million people in the United States. Although the direct harmful effects of alcohol in the liver are nearly universally recognized, emerging evidence suggests alcohol also adversely affects other organs such as the intestine, skeletal muscle, adipose tissue, and likely many other tissues. In fact, the extrahepatic effects of alcohol clearly converge to impact the morbidity and mortality associated with chronic alcohol abuse...
March 10, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28294298/proteins-and-chemical-chaperones-involved-in-neuronal-nicotinic-receptor-expression-and-function-an-update
#17
REVIEW
Arianna Crespi, Sara Francesca Colombo, Cecilia Gotti
Neuronal nicotinic acetylcholine receptors (nAChRs) are a family of acetylcholine-(ACh) gated cation channels and their homeostasis or proteostasis is essential for the correct physiology of the central and peripheral nervous systems. The proteostasis network regulates the folding, assembly, degradation and trafficking of nAChRs in order to ensure their efficient functional cell surface expression. However, as nAChRs are multisubunit, multispan, integral membrane proteins, the folding and assembly is a very inefficient process, and only a small portion of subunits can form functional pentamers...
March 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28292956/endoplasmic-reticulum-proteostasis-in-glioblastoma-from-molecular-mechanisms-to-therapeutic-perspectives
#18
REVIEW
Joanna Obacz, Tony Avril, Pierre-Jean Le Reste, Hery Urra, Véronique Quillien, Claudio Hetz, Eric Chevet
Cellular stress induced by the accumulation of misfolded proteins at the endoplasmic reticulum (ER) is a central feature of secretory cells and is observed in many tissues in various diseases, including cancer, diabetes, obesity, and neurodegenerative disorders. Cellular adaptation to ER stress is achieved by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that transmits information about the protein folding status at the ER to the cytosol and nucleus to restore proteostasis...
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28292901/bacterial-proteostasis-balances-energy-and-chaperone-utilization-efficiently
#19
Mantu Santra, Daniel W Farrell, Ken A Dill
Chaperones are protein complexes that help to fold and disaggregate a cell's proteins. It is not understood how four major chaperone systems of Escherichia coli work together in proteostasis: the recognition, sorting, folding, and disaggregating of the cell's many different proteins. Here, we model this machine. We combine extensive data on chaperoning, folding, and aggregation rates with expression levels of proteins and chaperones measured at different growth rates. We find that the proteostasis machine recognizes and sorts a client protein based on two biophysical properties of the client's misfolded state (M state): its stability and its kinetic accessibility from its unfolded state (U state)...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28287632/a-mammalian-nervous-system-specific-plasma-membrane-proteasome-complex-that-modulates-neuronal-function
#20
Kapil V Ramachandran, Seth S Margolis
In the nervous system, rapidly occurring processes such as neuronal transmission and calcium signaling are affected by short-term inhibition of proteasome function. It is unclear how proteasomes are able to acutely regulate such processes, as this action is inconsistent with their canonical role in proteostasis. Here we describe a mammalian nervous-system-specific membrane proteasome complex that directly and rapidly modulates neuronal function by degrading intracellular proteins into extracellular peptides that can stimulate neuronal signaling...
March 13, 2017: Nature Structural & Molecular Biology
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