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https://www.readbyqxmd.com/read/29107503/abrogating-mitochondrial-dynamics-in-mouse-hearts-accelerates-mitochondrial-senescence
#1
Moshi Song, Antonietta Franco, Julie A Fleischer, Lihong Zhang, Gerald W Dorn
Mitochondrial fusion and fission are critical to heart health; genetically interrupting either is rapidly lethal. To understand whether it is loss of, or the imbalance between, fusion and fission that underlies observed cardiac phenotypes, we engineered mice in which Mfn-mediated fusion and Drp1-mediated fission could be concomitantly abolished. Compared to fusion-defective Mfn1/Mfn2 cardiac knockout or fission-defective Drp1 cardiac knockout mice, Mfn1/Mfn2/Drp1 cardiac triple-knockout mice survived longer and manifested a unique pathological form of cardiac hypertrophy...
October 21, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29093165/sequences-flanking-the-transmembrane-segments-facilitate-mitochondrial-localization-and-membrane-fusion-by-mitofusin
#2
Xiaofang Huang, Xin Zhou, Xiaoyu Hu, Amit S Joshi, Xiangyang Guo, Yushan Zhu, Quan Chen, William A Prinz, Junjie Hu
Mitochondria constantly divide and fuse. Homotypic fusion of the outer mitochondrial membranes requires the mitofusin (MFN) proteins, a family of dynamin-like GTPases. MFNs are anchored in the membrane by transmembrane (TM) segments, exposing both the N-terminal GTPase domain and the C-terminal tail (CT) to the cytosol. This arrangement is very similar to that of the atlastin (ATL) GTPases, which mediate fusion of endoplasmic reticulum (ER) membranes. We engineered various MFN-ATL chimeras to gain mechanistic insight into MFN-mediated fusion...
November 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
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
#3
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/28713932/human-trypsin-inhibitor-reduces-the-apoptosis-of-lipopolysaccharide%C3%A2-induced-human-kidney%C3%A2-2-cells-by-promoting-mitochondrial-fusion
#4
Ning Liu, Zhiyi Jiang, Yongjun Liu, Yao Nie, Juan Chen, Bin Ouyang, Xiangdong Guan, Minying Chen
Imbalance in mitochondrial fusion/fission is one of the mechanisms leading to sepsis‑induced mitochondrial dysfunction and cell apoptosis. The present study examined the effects of human trypsin inhibitor (UTI), a well‑known antioxidant and anti‑inflammatory substance, on mitochondrial dynamics and cell apoptosis in lipopolysaccharide (LPS)‑induced human kidney‑2 (HK‑2) cells. The HK‑2 cells were incubated for 24 h either with LPS (800 ng/ml) or LPS (800 ng/ml) mixed with UTI (250 U/ml). Cell viability was assessed using a3‑(4,5‑dimethyl‑2‑thiazolyl)‑2, 5‑diphenyl‑2‑H‑tetrazolium bromide assay...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28676741/the-truncated-c-terminal-fragment-of-mutant-atxn3-disrupts-mitochondria-dynamics-in-spinocerebellar-ataxia-type-3-models
#5
Jung-Yu Hsu, Yu-Ling Jhang, Pei-Hsun Cheng, Yu-Fan Chang, Su-Han Mao, Han-In Yang, Chia-Wei Lin, Chuan-Mu Chen, Shang-Hsun Yang
Spinocerebellar ataxia type 3 (SCA3), known as Machado-Joseph disease, is an autosomal dominant disease caused by an abnormal expansion of polyglutamine in ATXN3 gene, leading to neurodegeneration in SCA3 patients. Similar to other neurodegenerative diseases, the dysfunction of mitochondria is observed to cause neuronal death in SCA3 patients. Based on previous studies, proteolytic cleavage of mutant ATXN3 is found to produce truncated C-terminal fragments in SCA3 models. However, whether these truncated mutant fragments disturb mitochondrial functions and result in pathological death is still unclear...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28623602/protein-requirements-of-collared-peccary-pecari-tajacu
#6
Rogério M Borges, Alcester Mendes, Selene S C Nogueira, Jérôme Bindelle, Sérgio L G Nogueira-Filho
A nitrogen (N) balance digestion trial was conducted to determine the protein requirement of collared peccaries (Pecari tajacu). In a 4 × 4 Latin square design, four captive adult male peccaries were fed four isoenergy diets containing four different levels of N (11.7, 16.3, 22.8, and 26.7 g N/kg of dry matter-DM). After 15 days of adaptation, a total collection of feces and urine was carried out for five consecutive days. Regression analyses between N intake and N in feces and urine allowed to calculate the metabolic fecal nitrogen (MFN = 2...
October 2017: Tropical Animal Health and Production
https://www.readbyqxmd.com/read/28404953/hydrogen-rich-saline-attenuates-spinal-cord-hemisection-induced-testicular-injury-in-rats
#7
Li Ge, Li-Hua Wei, Chang-Qing Du, Guo-Hua Song, Ya-Zhuo Xue, Hao-Shen Shi, Ming Yang, Xin-Xin Yin, Run-Ting Li, Xue-Er Wang, Zhen Wang, Wen-Gang Song
To study how hydrogen-rich saline (HS) promotes the recovery of testicular biological function in a hemi-sectioned spinal cord injury (hSCI) rat model, a right hemisection was performed at the T11-T12 of the spinal cord in Wistar rats. Animals were divided into four groups: normal group; vehicle group: sham-operated rats administered saline; hSCI group: subjected to hSCI and administered saline; HRST group: subjected to hSCI and administered HS. Hind limb neurological function, testis index, testicular morphology, mean seminiferous tubular diameter (MSTD) and seminiferous epithelial thickness (MSET), the expression of heme oxygenase-1 (HO-1), mitofusin-2 (MFN-2), and high-mobility group box 1 (HMGB-1), cell ultrastructure, and apoptosis of spermatogenic cells were studied...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402477/coercive-and-legitimate-authority-impact-tax-honesty-evidence-from-behavioral-and-erp-experiments
#8
Katharina Gangl, Daniela M Pfabigan, Claus Lamm, Erich Kirchler, Eva Hofmann
Cooperation in social systems such as tax honesty is of central importance in our modern societies. However, we know little about cognitive and neural processes driving decisions to evade or pay taxes. This study focuses on the impact of perceived tax authority and examines the mental chronometry mirrored in ERP data allowing a deeper understanding about why humans cooperate in tax systems. We experimentally manipulated coercive and legitimate authority and studied its impact on cooperation and underlying cognitive (experiment 1, 2) and neuronal (experiment 2) processes...
July 1, 2017: Social Cognitive and Affective Neuroscience
https://www.readbyqxmd.com/read/28384228/doxycycline-protects-against-ros-induced-mitochondrial-fragmentation-and-iso-induced-heart-failure
#9
Adam Riba, Laszlo Deres, Krisztian Eros, Aliz Szabo, Klara Magyar, Balazs Sumegi, Kalman Toth, Robert Halmosi, Eszter Szabados
In addition to their anti-bacterial action, tetracyclines also have complex biological effects, including the modification of mitochondrial protein synthesis, metabolism and gene-expression. Long-term clinical studies have been performed using tetracyclines, without significant side effects. Previous studies demonstrated that doxycycline (DOX), a major tetracyclin antibiotic, exerted a protective effect in animal models of heart failure; however, its exact molecular mechanism is still unknown. Here, we provide the first evidence that DOX reduces oxidative stress-induced mitochondrial fragmentation and depolarization in H9c2 cardiomyocytes and beneficially alters the expression of Mfn-2, OPA-1 and Drp-1 -the main regulators of mitochondrial fusion and fission-in our isoproterenol (ISO)-induced heart failure model, ultimately decreasing the severity of heart failure...
2017: PloS One
https://www.readbyqxmd.com/read/28356916/spasmolytic-and-antibacterial-activity-of-two-citrus-sinensis-osbeck-varieties-cultivated-in-mexico
#10
Amanda Sánchez-Recillas, Ana Ly Arroyo-Herrera, Jesús Alfredo Araujo-León, Emanuel Hernández Núñez, Rolffy Ortiz Andrade
Antibacterial activity on ATCC strains of Escherichia coli, Salmonella enterica, Salmonella enteritidis, and Salmonella choleraesuis and spasmolytic effect on contraction on rat ileum trips were determinate. Eight organic extracts (hexanic and methanolic) of albedo (mesocarp) and flavedo (pericarp) of two varieties (Valencian and National) of Citrus sinensis (L.) Osbeck of Yucatán, México, were studied. Additionally, chromatographic fingerprints were obtained and correlated with their pharmacological effects...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28154412/superresolution-imaging-identifies-that-conventional-trafficking-pathways-are-not-essential-for-endoplasmic-reticulum-to-outer-mitochondrial-membrane-protein-transport
#11
Kyle Salka, Shivaprasad Bhuvanendran, Kassandra Wilson, Petros Bozidis, Mansi Mehta, Kristin Rainey, Hiromi Sesaki, George H Patterson, Jyoti K Jaiswal, Anamaris M Colberg-Poley
Most nuclear-encoded mitochondrial proteins traffic from the cytosol to mitochondria. Some of these proteins localize at mitochondria-associated membranes (MAM), where mitochondria are closely apposed with the endoplasmic reticulum (ER). We have previously shown that the human cytomegalovirus signal-anchored protein known as viral mitochondria-localized inhibitor of apoptosis (vMIA) traffics from the ER to mitochondria and clusters at the outer mitochondrial membrane (OMM). Here, we have examined the host pathways by which vMIA traffics from the ER to mitochondria and clusters at the OMM...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27998959/exogenous-h2s-regulates-endoplasmic-reticulum-mitochondria-cross-talk-to-inhibit-apoptotic-pathways-in-stz-induced-type-i-diabetes
#12
Fan Yang, Xiangjing Yu, Ting Li, Jianjun Wu, Yajun Zhao, Jiaqi Liu, Aili Sun, Shiyun Dong, Jichao Wu, Xin Zhong, Changqing Xu, Fanghao Lu, Weihua Zhang
The upregulation of reactive oxygen species (ROS) is a primary cause of cardiomyocyte apoptosis in diabetes cardiomyopathy (DCM). Mitofusin-2 (Mfn-2) is a key protein that bridges the mitochondria and endoplasmic reticulum (ER). Hydrogen sulfide (H2S)-mediated cardioprotection is related to antioxidant effects. The present study demonstrated that H2S inhibited the interaction between the ER and mitochondrial apoptotic pathway. This study investigated cardiac function, ultrastructural changes in the ER and mitochondria, apoptotic rate using TUNEL, and the expression of ER stress-associated proteins and mitochondrial apoptotic proteins in cardiac tissues in STZ-induced type I diabetic rats treated with or without NaHS (donor of H2S)...
March 1, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27920125/structures-of-human-mitofusin-1-provide-insight-into-mitochondrial-tethering
#13
Yuanbo Qi, Liming Yan, Caiting Yu, Xiangyang Guo, Xin Zhou, Xiaoyu Hu, Xiaofang Huang, Zihe Rao, Zhiyong Lou, Junjie Hu
Mitochondria undergo fusion and fission. The merging of outer mitochondrial membranes requires mitofusin (MFN), a dynamin-like GTPase. How exactly MFN mediates membrane fusion is poorly understood. Here, we determined crystal structures of a minimal GTPase domain (MGD) of human MFN1, including the predicted GTPase and the distal part of the C-terminal tail (CT). The structures revealed that a helix bundle (HB) formed by three helices extending from the GTPase and one extending from the CT closely attaches to the GTPase domain, resembling the configuration of bacterial dynamin-like protein...
December 5, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27913356/a-framework-for-integrating-multiple-biological-networks-to-predict-microrna-disease-associations
#14
Wei Peng, Wei Lan, Zeng Yu, Jianxin Wang, Yi Pan
MicroRNAs have close relationship with human diseases. Therefore, identifying disease related MicroRNAs plays an important role in disease diagnosis, prognosis and therapy. However, designing an effective computational method which can make good use of various biological resources and correctly predict the associations between MicroRNA and disease is still a big challenge. Previous researchers have pointed out that there are complex relationships among microRNAs, diseases and environment factors. There are inter-relationships between microRNAs, diseases or environment factors based on their functional similarity or phenotype similarity or chemical structure similarity and so on...
March 2017: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/27881711/mitochondrial-fusion-reaching-the-end-of-mitofusin-s-tether
#15
Luke E Formosa, Michael T Ryan
In this issue, Qi et al. (2016. J. Cell Biol https://doi.org/10.1083/jcb.201609019) provide structural insights into the mechanisms of mitochondrial outer membrane fusion by investigating the structure of mitofusin 1 (MFN1). This work proposes a new model to explain the important and elusive process of MFN-mediated mitochondrial fusion.
December 5, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27801955/curcumin-prevents-mitochondrial-dynamics-disturbances-in-early-5-6-nephrectomy-relation-to-oxidative-stress-and-mitochondrial-bioenergetics
#16
Omar Emiliano Aparicio-Trejo, Edilia Tapia, Eduardo Molina-Jijón, Omar Noel Medina-Campos, Norma Angélica Macías-Ruvalcaba, Juan Carlos León-Contreras, Rogelio Hernández-Pando, Fernando E García-Arroyo, Magdalena Cristóbal, Laura Gabriela Sánchez-Lozada, José Pedraza-Chaverri
Five-sixths nephrectomy (5/6NX) is a widely used model to study the mechanisms leading to renal damage in chronic kidney disease (CKD). However, early alterations on renal function, mitochondrial dynamics, and oxidative stress have not been explored yet. Curcumin is an antioxidant that has shown nephroprotection in 5/6NX-induced renal damage. The aim of this study was to explore the effect of curcumin on early mitochondrial alterations induced by 5/6NX in rats. In isolated mitochondria, 5/6NX-induced hydrogen peroxide production was associated with decreased activity of complexes I and V, decreased activity of antioxidant enzymes, alterations in oxygen consumption and increased MDA-protein adducts...
March 2017: BioFactors
https://www.readbyqxmd.com/read/27775718/correcting-mitochondrial-fusion-by-manipulating-mitofusin-conformations
#17
Antonietta Franco, Richard N Kitsis, Julie A Fleischer, Evripidis Gavathiotis, Opher S Kornfeld, Guohua Gong, Nikolaos Biris, Ann Benz, Nir Qvit, Sara K Donnelly, Yun Chen, Steven Mennerick, Louis Hodgson, Daria Mochly-Rosen, Gerald W Dorn
Mitochondria are dynamic organelles that exchange contents and undergo remodelling during cyclic fusion and fission. Genetic mutations in MFN2 (the gene encoding mitofusin 2) interrupt mitochondrial fusion and cause the untreatable neurodegenerative condition Charcot-Marie-Tooth disease type 2A (CMT2A). It has not yet been possible to directly modulate mitochondrial fusion, in part because the structural basis of mitofusin function is not completely understood. Here we show that mitofusins adopt either a fusion-constrained or a fusion-permissive molecular conformation, directed by specific intramolecular binding interactions, and demonstrate that mitofusin-dependent mitochondrial fusion can be regulated in mouse cells by targeting these conformational transitions...
December 1, 2016: Nature
https://www.readbyqxmd.com/read/27734234/mangiferin-inhibits-il-1%C3%AE-induced-inflammatory-response-by-activating-ppar-%C3%AE-in-human-osteoarthritis-chondrocytes
#18
Yanlong Qu, Li Zhou, Chunlei Wang
Inflammation has been reported to play critical roles in the development of osteoarthritis. In the present study, we investigated whether mangiferin (MFN) had anti-inflammatory effects in IL-1β-stimulated human osteoarthritis chondrocytes. The cells were treated with various concentrations of MFN in the presence or absence of IL-1β. The production of MMP-1, MMP-3, PGE2, and NO was measured in this study. The expression of NF-kB and PPAR-γ was detected by western blot analysis. MFN inhibited IL-1β-induced inflammatory mediators PGE2 and NO production...
February 2017: Inflammation
https://www.readbyqxmd.com/read/27647893/critical-reappraisal-confirms-that-mitofusin-2-is-an-endoplasmic-reticulum-mitochondria-tether
#19
Deborah Naon, Marta Zaninello, Marta Giacomello, Tatiana Varanita, Francesca Grespi, Sowmya Lakshminaranayan, Annalisa Serafini, Martina Semenzato, Stephanie Herkenne, Maria Isabel Hernández-Alvarez, Antonio Zorzano, Diego De Stefani, Gerald W Dorn, Luca Scorrano
The discovery of the multiple roles of mitochondria-endoplasmic reticulum (ER) juxtaposition in cell biology often relied upon the exploitation of Mitofusin (Mfn) 2 as an ER-mitochondria tether. However, this established Mfn2 function was recently questioned, calling for a critical re-evaluation of Mfn2's role in ER-mitochondria cross-talk. Electron microscopy and fluorescence-based probes of organelle proximity confirmed that ER-mitochondria juxtaposition was reduced by constitutive or acute Mfn2 deletion...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27623243/regulation-of-mitoflash-biogenesis-and-signaling-by-mitochondrial-dynamics
#20
Wenwen Li, Tao Sun, Beibei Liu, Di Wu, Wenfeng Qi, Xianhua Wang, Qi Ma, Heping Cheng
Mitochondria are highly dynamic organelles undergoing constant network reorganization and exhibiting stochastic signaling events in the form of mitochondrial flashes (mitoflashes). Here we investigate whether and how mitochondrial network dynamics regulate mitoflash biogenesis and signaling. We found that mitoflash frequency was largely invariant when network fragmentized or redistributed in the absence of mitofusin (Mfn) 1, Mfn2, or Kif5b. However, Opa1 deficiency decreased spontaneous mitoflash frequency due to superimposing changes in respiratory function, whereas mitoflash response to non-metabolic stimulation was unchanged despite network fragmentation...
2016: Scientific Reports
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