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https://www.readbyqxmd.com/read/28810752/rupturing-the-hemi-fission-intermediate-in-membrane-fission-under-tension-reaction-coordinates-kinetic-pathways-and-free-energy-barriers
#1
Guojie Zhang, Marcus Müller
Membrane fission is a fundamental process in cells, involved inter alia in endocytosis, intracellular trafficking, and virus infection. Its underlying molecular mechanism, however, is only incompletely understood. Recently, experiments and computer simulation studies have revealed that dynamin-mediated membrane fission is a two-step process that proceeds via a metastable hemi-fission intermediate (or wormlike micelle) formed by dynamin's constriction. Importantly, this hemi-fission intermediate is remarkably metastable, i...
August 14, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28808055/dynamin-dependent-amino-acid-endocytosis-activates-mechanistic-target-of-rapamycin-complex-1-mtorc1
#2
Shusaku Shibutani, Hana Okazaki, Hiroyuki Iwata
The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of protein synthesis and potential target for modifying cellular metabolism in various conditions, including cancer and aging. mTORC1 activity is tightly regulated by the availability of extracellular amino acids, and previous studies have revealed that amino acids in the extracellular fluid are transported to the lysosomal lumen. There, amino acids induce recruitment of cytoplasmic mTORC1 to the lysosome by the Rag GTPases, followed by mTORC1 activation by the small GTPase Ras homolog enriched in brain (Rheb)...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28803609/comic-the-hidden-dynamics-of-mitochondrial-inner-compartments
#3
Bongki Cho, Woong Sun
Mitochondria have evolutionarily, functionally and structurally distinct outer- (OMM) and inner-membranes (IMM). Thus, mitochondrial morphology is controlled by independent but coordinated activity of fission and fusion of the OMM and IMM. Constriction and division of the OMM are mediated by endocytosis-like machineries, which include dynamin-related protein 1 with additional cytosolic vesicle scissoring machineries such as actin filament and Dynamin 2. However, structural alteration of the IMM during mitochondrial division has been poorly understood...
August 14, 2017: BMB Reports
https://www.readbyqxmd.com/read/28790323/mitochondrial-division-inhibitor-1-is-neuroprotective-in-the-a53t-%C3%AE-synuclein-rat-model-of-parkinson-s-disease
#4
Simone Bido, Federico N Soria, Rebecca Z Fan, Erwan Bezard, Kim Tieu
Alpha-synuclein (α-syn) is involved in both familial and sporadic Parkinson's disease (PD). One of the proposed pathogenic mechanisms of α-syn mutations is mitochondrial dysfunction. However, it is not entirely clear the impact of impaired mitochondrial dynamics induced by α-syn on neurodegeneration and whether targeting this pathway has therapeutic potential. In this study we evaluated whether inhibition of mitochondrial fission is neuroprotective against α-syn overexpression in vivo. To accomplish this goal, we overexpressed human A53T-α- synuclein (hA53T-α-syn) in the rat nigrostriatal pathway, with or without treatment using the small molecule Mitochondrial Division Inhibitor-1 (mdivi-1), a putative inhibitor of the mitochondrial fission Dynamin-Related Protein-1 (Drp1)...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790012/mdivi-1-ameliorates-early-brain-injury-after-subarachnoid-hemorrhage-via-the-suppression-of-inflammation-related-blood-brain-barrier-disruption-and-endoplasmic-reticulum-stress-based-apoptosis
#5
Lin-Feng Fan, Ping-You He, Yu-Cong Peng, Qing-Hua Du, Yi-Jun Ma, Jian-Xiang Jin, Hang-Zhe Xu, Jian-Ru Li, Zhi-Jiang Wang, Sheng-Long Cao, Tao Li, Feng Yan, Chi Gu, Lin Wang, Gao Chen
Aberrant modulation of mitochondrial dynamic network, which shifts the balance of fusion and fission towards fission, is involved in brain damage of various neurodegenerative diseases including Parkinson's disease, Huntington's disease and Alzheimer's disease. A recent research has shown that the inhibition of mitochondrial fission alleviates early brain injury after experimental subarachnoid hemorrhage, however, the underlying molecular mechanisms have remained to be elucidated. This study was undertaken to characterize the effects of the inhibition of dynamin-related protein-1 (Drp1, a dominator of mitochondrial fission) on blood-brain barrier (BBB) disruption and neuronal apoptosis following SAH and the potential mechanisms...
August 5, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28769084/antibody-induced-dimerization-of-fgfr1-promotes-receptor-endocytosis-independently-of-its-kinase-activity
#6
Łukasz Opaliński, Aleksandra Sokołowska-Wędzina, Martyna Szczepara, Małgorzata Zakrzewska, Jacek Otlewski
Fibroblast growth factors (FGFs) and their plasma membrane-localized receptors (FGFRs) play a key role in the regulation of developmental processes and metabolism. Aberrant FGFR signaling is associated with the progression of serious metabolic diseases and human cancer. Binding of FGFs to FGFRs induces receptor dimerization and transphosphorylation of FGFR kinase domains that triggers activation of intracellular signaling pathways. Following activation, FGFRs undergo internalization and subsequent lysosomal degradation, which terminates transmission of signals...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28767702/astragaloside-iv-ameliorates-diabetic-nephropathy-by-modulating-the-mitochondrial-quality-control-network
#7
Xinhui Liu, Wenjing Wang, Gaofeng Song, Xian Wei, Youjia Zeng, Pengxun Han, Dongtao Wang, Mumin Shao, Juan Wu, Huili Sun, Guoliang Xiong, Shunmin Li
The aim of this study was to investigate the effect and possible mechanism of Astragaloside IV (AS-IV) on retarding the progression of diabetic nephropathy (DN) in a type 2 diabetic animal model, db/db mice. Eight-week-old male db/db diabetic mice and their nondiabetic littermate control db/m mice were used in the present study. AS-IV was administered to the db/db mice by adding it to standard feed at a dose of 1g/kg for 12 weeks. Renal injury was assessed by urinary albumin excretion (UAE) and Periodic acid-Schiff staining...
2017: PloS One
https://www.readbyqxmd.com/read/28765603/predictions-of-backbone-dynamics-in-intrinsically-disordered-proteins-using-de-novo-fragment-based-protein-structure-predictions
#8
Tomasz Kosciolek, Daniel W A Buchan, David T Jones
Intrinsically disordaered proteins (IDPs) are a prevalent phenomenon with over 30% of human proteins estimated to have long disordered regions. Computational methods are widely used to study IDPs, however, nearly all treat disorder in a binary fashion, not accounting for the structural heterogeneity present in disordered regions. Here, we present a new de novo method, FRAGFOLD-IDP, which addresses this problem. Using 200 protein structural ensembles derived from NMR, we show that FRAGFOLD-IDP achieves superior results compared to methods which can predict related data (NMR order parameter, or crystallographic B-factor)...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28761175/rock1-is-a-novel-rac1-effector-to-regulate-tubular-endocytic-membrane-formation-during-clathrin-independent-endocytosis
#9
David Soriano-Castell, Albert Chavero, Carles Rentero, Marta Bosch, Maite Vidal-Quadras, Albert Pol, Carlos Enrich, Francesc Tebar
Clathrin-dependent and -independent pathways contribute for β1-integrin endocytosis. This study defines a tubular membrane clathrin-independent endocytic network, induced with the calmodulin inhibitor W13, for β1-integrin internalization. This pathway is dependent on increased phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) levels and dynamin activity at the plasma membrane. Exogenous addition of PI(4,5)P2 or phosphatidylinositol-4-phosphate 5-kinase (PIP5K) expression mimicked W13-generated-tubules which are inhibited by active Rac1...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28761019/effects-of-trimetazidine-on-mitochondrial-respiratory-function-biosynthesis-and-fission-fusion-in-rats-with-acute-myocardial-ischemia
#10
Wen Shi, Wenfeng Shangguan, Yue Zhang, Can Li, Guangping Li
OBJECTIVE: Myocardial ischemia affects mitochondrial functions, leading to ionic imbalance and susceptibility to ventricular fibrillation. Trimetazidine, a metabolic agent, is clinically used in anti-anginal therapy. METHODS: In this study, the rats were orally treated by gavage with trimetazidine 10 mg/kg/d for 7 days, and the effects of trimetazidine on mitochondrial respiratory function, biosynthesis, and fission/fusion in rats with acute myocardial ischemia were evaluated...
July 25, 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/28754444/mitochondrial-dynamics-the-dynamin-superfamily-and-execution-by-collusion
#11
REVIEW
Rajesh Ramachandran
Distinct dynamin superfamily GTPases catalyze the constant fission and fusion of the elaborate mitochondrial networks that navigate the eukaryotic cytoplasm. Long believed to be the singular handiwork of dynamin-related protein 1 (Drp1), a cytosolic family member that transiently localizes to the mitochondrial surface, the execution of mitochondrial fission is now arguably believed to entail membrane remodeling events that are initiated upstream of Drp1 by ER-associated cytoskeletal networks and completed downstream by the prototypical dynamin, dynamin 2 (Dyn2)...
July 25, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28750371/mitochondrial-fission-inhibitors-suppress-endothelin-1-induced-artery-constriction
#12
Chang Chen, Jin-Lai Gao, Ming-Yu Liu, Shan-Liang Li, Xiu-Chen Xuan, Xin-Zi Zhang, Xi-Yue Zhang, Yuan-Yuan Wei, Chang-Lin Zhen, Jing Jin, Xin Shen, De-Li Dong
BACKGROUND/AIMS: Endothelin-1 is implicated in the pathogenesis of hypertension, but the underlying mechanisms remained elusive. Our previous study found that inhibition of mitochondrial fission of smooth muscle cells suppressed phenylephrine- and high K+-induced artery constriction. Here, we studied the effects of mitochondrial fission inhibitors on endothelin-1-induced vasoconstriction. METHODS: The tension of rat mesenteric arteries and thoracic aorta was measured by using a multi-wire myograph system...
July 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28745416/a-role-for-host-cell-exocytosis-in-inlb-mediated-internalization-of-listeria-monocytogenes
#13
Hoan Van Ngo, Manmeet Bhalla, Da-Yuan Chen, Keith Ireton
The bacterial surface protein InlB mediates internalization of Listeria monocytogenes into human cells through interaction with the host receptor tyrosine kinase, Met. InlB-mediated entry requires localized polymerization of the host actin cytoskeleton. Apart from actin polymerization, roles for other host processes in Listeria entry are unknown. Here we demonstrate that exocytosis in the human cell promotes InlB-dependent internalization. Using a probe consisting of VAMP3 with an exofacial Green Fluorescent Protein (GFP) tag, focal exocytosis was detected during InlB-mediated entry...
July 26, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28743390/baicalin-attenuates-in-vivo-and-in-vitro-hyperglycemia-exacerbated-ischemia-reperfusion-injury-by-regulating-mitochondrial-function-in-a-manner-dependent-on-ampk
#14
Shanshan Li, Xiaoxu Sun, Lixing Xu, Ruoxi Sun, Zhanqiang Ma, Xueyang Deng, Baolin Liu, Qiang Fu, Rong Qu, Shiping Ma
Cerebral ischemia/reperfusion (I/R) is a lethal and disabling disease. Studies have suggested that hyperglycemia is a risk factor for cerebral I/R. Baicalin is a natural bioactive flavonoid extracted from Scutellaria baicalensis Georgi with neuroprotective activity. In the present study, we investigated the effects of baicalin on hyperglycemia-exacerbated cerebral I/R injury. Streptozotocin (STZ) injection aggravated the brain damage induced by middle cerebral artery occlusion (MCAO) surgery, while baicalin administration reduced blood glucose, relieved neurological deficit and decreased infarct volume...
July 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28741080/transcriptomic-analyses-reveal-clathrin-mediated-endocytosis-involved-in-symbiotic-seed-germination-of-gastrodia-elata
#15
Xu Zeng, Yuanyuan Li, Hong Ling, Sisi Liu, Mengmeng Liu, Juan Chen, Shunxing Guo
BACKGROUND: Gastrodia elata is a well-known medicinal orchid. In nature, the germination rate of G. elata is extremely poor, because there is no endosperm within the mature seed. It is crucial for G. elata to obtain nutrition from mycorrhizal fungi (Mycena) at the early-stage of germination. After germination, the seed gives rise to a protocorm. However, there are no "omic" studies on understanding the interaction between Gastrodia and Mycena. Here, we used transcriptomic approaches to explore changes in seed germination of G...
December 2017: Botanical Studies (Taipei, Taiwan)
https://www.readbyqxmd.com/read/28740838/a-rare-case-of-centronuclear-myopathy-with-dnm2-mutation-genotype-phenotype-correlation
#16
REVIEW
Amir Ghorbani Aghbolaghi, Mirna Lechpammer
Centronuclear myopathy (CNM) is a group of rare genetic muscle disorders characterized by muscle fibers with centrally located nuclei. The most common forms of CNM have been attributed to X-linked recessive mutations in the MTM1 gene; autosomal-dominant mutations in the DNM2 gene-encoding dynamin-2, the BIN1 gene; and autosomal-recessive mutations in BIN1, RYR1, and TTN genes. Dominant CNM due to DNM2 mutations usually follows a mild clinical course with the onset in adolescence. Currently, around 35 mutations of the DNM2 gene have been identified in CNM; however, the underlying molecular mechanism of DNM2 mutation in the pathology of CNM remains elusive, and the standard clinical characteristics have not yet been defined...
April 2017: Autopsy & case reports
https://www.readbyqxmd.com/read/28729291/stimulator-of-ifn-genes-mediated-dna-sensing-pathway-is-suppressed-by-nlrp3-agonists-and-regulated-by-mitofusin-1-and-tbc1d15-mitochondria-dynamics-mediators
#17
Dohyeong Kwon, Eunbyeol Park, Suk-Jo Kang
The stimulator of IFN genes (STING)-mediated DNA-sensing pathway plays an important role in the innate immune response to pathogen infection, autoimmunity, and cancer; however, its regulatory mechanism has not been fully elucidated, and we do not yet know whether the STING pathway is counter-regulated by other innate immune pathways. Here, we show that the NLRP3-activating agonists, ATP and nigericin, prevent STING pathway activation in association with mitochondrial fragmentation; however, the suppression of the STING pathway and mitochondria fission were not dependent on NLRP3 or potassium efflux...
July 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28724764/rab5-and-rab11-are-required-for-clathrin-dependent-endocytosis-of-japanese-encephalitis-virus-in-bhk-21-cells
#18
Chun-Chun Liu, Yun-Na Zhang, Zhao-Yao Li, Jin-Xiu Hou, Jing Zhou, Lin Kan, Bin Zhou, Pu-Yan Chen
During infection Japanese Encephalitis Virus generally enters host cells via receptor-mediated clathrin dependent endocytosis. The trafficking of JEV within endosomes is controlled by Rab GTPases, but which Rab proteins are involved in JEV entry into BHK-21 cells is unknown. In this study, entry and post-internalization of JEV were analyzed using biochemical inhibitors, RNA interference and dominant negative mutants. Our data demonstrate that JEV entry into BHK-21 cells depends on clathrin, dynamin, and cholesterol, but not caveolae or macropinocytosis...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28718976/low-density-lipopolyprotein-inhibits-flavivirus-acquisition-in-aedes-aegypti
#19
Z L Wagar, M O Tree, M C Mpoy, M J Conway
Aedes aegypti is the primary vector of a number of human pathogens including dengue virus (DENV) and Zika virus (ZIKV). Ae. aegypti acquires these viruses during the processing of bloodmeals obtained from an infected vertebrate host. Vertebrate blood contains a number of factors that have the potential to modify virus acquisition in the mosquito. Interestingly, low density lipopolyprotein (LDL) levels are decreased during severe DENV infection. Accordingly, we hypothesized that LDL is a modifiable factor that can influence flavivirus acquisition in the mosquito...
July 18, 2017: Insect Molecular Biology
https://www.readbyqxmd.com/read/28712398/-fasudil-attenuates-mitochondrial-injury-and-apoptosis-in-rat-model-of-myocardial-ischemia-reperfusion-injury
#20
Hongwei Ye, Guanjun Zhang, Ruiping Cao, Pinfang Kang, Zhenghong Li, Qin Gao
Objective To observe the changes of mitochondria fusion protein 2 (Mfn2) and dynamin-related protein 1 (Drp1) in the cardioprotection of fasudil, and analyze the significance. Methods Hearts isolated from male Sprague-Dawley rats were subjected to ischemia for 30 minutes (occlusion of left anterior descending artery), and continuously perfusion for 120 minutes to establish myocardial ischemia/reperfusion (I/R) injury model. The rats were divided into 3 groups: sham group, I/R group and fasudil group. The left ventricular hemodynamics were continuously recorded; lactate dehydrogenase (LDH) content was measured during reperfusion; myocardial ultrastructure was observed by electron microscopy; the protein expression of phosphorylated protein phosphatase 1 regulatory subunit 12A (p-PPP1R12A/p-MYPT1) was detected by immunohistochemistry; and the protein expressions of Mfn2, Drp1 and cleaved caspase-3 (c-caspase-3) were detected by Western blot analysis...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
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