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https://www.readbyqxmd.com/read/29125827/early-cerebellar-deficits-in-mitochondrial-biogenesis-and-respiratory-chain-complexes-in-the-kiko-mouse-model-of-friedreich-ataxia
#1
Hong Lin, Jordi Magrane, Amy Rattelle, Anna Stepanova, Alexander Galkin, Elisia M Clark, Yi Na Dong, Sarah M Halawani, David R Lynch
Friedreich ataxia (FRDA), the most common recessive inherited ataxia, results from deficiency of frataxin, a small mitochondrial protein crucial for iron-sulphur cluster formation and ATP production. Frataxin deficiency is associated with mitochondrial dysfunction in FRDA patients and animal models; however, early mitochondrial pathology in FRDA cerebellum remains elusive. Using frataxin knock-in/knockout (KIKO) mice and KIKO mice carrying the mitoDendra transgene, we show early cerebellar deficits in mitochondrial biogenesis and respiratory chain complexes in this FRDA model...
November 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29097872/mitofusin-2-mediated-mitochondrial-ca-2-uptake-1-2-induced-liver-injury-in-rat-remote-ischemic-perconditioning-liver-transplantation-and-alpha-mouse-liver-12-hypoxia-cell-line-models
#2
Ruo-Peng Liang, Jun-Jun Jia, Jian-Hui Li, Ning He, Yan-Fei Zhou, Li Jiang, Tao Bai, Hai-Yang Xie, Lin Zhou, Yu-Ling Sun
AIM: To investigate the protective mechanism of mitofusin-2 (Mfn2) in rat remote ischemic perconditioning (RIC) models and revalidate it in alpha mouse liver-12 (AML-12) hypoxia cell lines. METHODS: Sprague-Dawley rats were divided into three groups (n = 6 each): sham, orthotopic liver transplantation and RIC. After operation, blood samples were collected to test alanine aminotransferase and aspartate aminotransferase. The liver lobes were harvested for histopathological examination, western blotting (WB) and quantitative real-time (qRT)-PCR...
October 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29093165/sequences-flanking-the-transmembrane-segments-facilitate-mitochondrial-localization-and-membrane-fusion-by-mitofusin
#3
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/29068134/structure-function-and-regulation-of-mitofusin-2-in-health-and-disease
#4
Gursimran Chandhok, Michael Lazarou, Brent Neumann
Mitochondria are highly dynamic organelles that constantly migrate, fuse, and divide to regulate their shape, size, number, and bioenergetic function. Mitofusins (Mfn1/2), optic atrophy 1 (OPA1), and dynamin-related protein 1 (Drp1), are key regulators of mitochondrial fusion and fission. Mutations in these molecules are associated with severe neurodegenerative and non-neurological diseases pointing to the importance of functional mitochondrial dynamics in normal cell physiology. In recent years, significant progress has been made in our understanding of mitochondrial dynamics, which has raised interest in defining the physiological roles of key regulators of fusion and fission and led to the identification of additional functions of Mfn2 in mitochondrial metabolism, cell signalling, and apoptosis...
October 25, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/29034772/opa-interacting-protein-5-modulates-docetaxel-induced-cell-death-via-regulation-of-mitophagy-in-gastric-cancer
#5
Tae Woo Kim, Seon-Jin Lee, Young-Jun Park, Sang Yoon Park, Byung Moo Oh, Yun Sun Park, Bo-Yeon Kim, Young-Ha Lee, Hee Jun Cho, Suk Ran Yoon, Yong-Kyung Choe, Hee Gu Lee
Damage to mitochondria induces mitophagy, a cellular process that is gaining interest for its therapeutic relevance to a variety of human diseases. However, the mechanism underlying mitochondrial depolarization and clearance in mitophagy remains poorly understood. We previously reported that mitochondria-induced cell death was caused by knockdown of Neisseria gonorrhoeae opacity-associated-interacting protein 5 in gastric cancer. In this study, we show that Neisseria gonorrhoeae opacity-associated-interacting protein 5 loss and gain of function modulates mitophagy induced by treatment with docetaxel, a chemotherapy drug for gastric cancer...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29028772/heme-oxygenase-1-protects-the-liver-from-septic-injury-by-modulating-tlr4-mediated-mitochondrial-quality-control-in-mice
#6
Jin-Sook Park, Hyo-Sun Choi, So-Yeon Yim, Sun-Mee Lee
Mitochondrial dysfunction is involved in the pathogenesis of sepsis-induced multiple organ dysfunction syndrome (MODS). Mitochondrial quality control (QC) is characterized by self-recovering mitochondrial damage through mitochondrial biogenesis, mitophagy, and fission/fusion. Heme oxygenase (HO)-1 acts as a signaling molecule to modulate inflammation. The present study elucidated the cytoprotective mechanisms of HO-1 in sepsis, particularly focusing on toll-like receptor (TLR)4-mediated mitochondrial QC. Mice were subjected to sepsis by cecal ligation and puncture (CLP)...
October 12, 2017: Shock
https://www.readbyqxmd.com/read/28993979/methamphetamine-augments-concurrent-astrocyte-mitochondrial-stress-oxidative-burden-and-antioxidant-capacity-tipping-the-balance-in-hiv-associated-neurodegeneration
#7
Kathleen Borgmann, Anuja Ghorpade
Methamphetamine (METH) use, with and without human immunodeficiency virus (HIV)-1 comorbidity, exacerbates neurocognitive decline. Oxidative stress is a probable neurotoxic mechanism during HIV-1 central nervous system infection and METH abuse, as viral proteins, antiretroviral therapy and METH have each been shown to induce mitochondrial dysfunction. However, the mechanisms regulating mitochondrial homeostasis and overall oxidative burden in astrocytes are not well understood in the context of HIV-1 infection and METH abuse...
October 9, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28990868/prevention-of-recognition-memory-loss-and-moderation-of-mitochondrial-dynamic-tendency-toward-fusion-by-flavone-derivatives-in-a%C3%AE-injected-rats-a-comparison-between-two-flavonoids-with-different-polarity
#8
Farshad Arsalandeh, Fariba Khodagholi, Shahin Ahmadian, Forough Foolad, Hamed Mohammadi Kamsorkh, Mahdi Moridi Farimani, Fatemeh Shaerzadeh
Growing evidence sheds light on the use of flavonoids as the promising alternatives for the treatment of chronic conditions, including cancer and neurodegenerative disorders. Accordingly, in the present study, we aimed at evaluating the effects of oral intake of two structurally different flavonoids 5-hydroxy-6,7,4'-trimethoxyflavone (flavone 1) and 5,7,4'-trihydroxyflavone (flavone 2) on recognition memory, hippocampal protein level of immediate early gene cFos and mitochondrial dynamic markers in Amyloid β (Aβ)-injected rats...
October 9, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28977005/renal-cold-storage-followed-by-transplantation-impairs-expression-of-key-mitochondrial-fission-and-fusion-proteins
#9
Nirmala Parajuli, Stephen Shrum, Julia Tobacyk, Alex Harb, John M Arthur, Lee Ann MacMillan-Crow
BACKGROUND: The majority of transplanted kidneys are procured from deceased donors which all require exposure to cold storage (CS) for successful transplantation. Unfortunately, this CS leads to renal and mitochondrial damage but, specific mitochondrial targets affected by CS remain largely unknown. The goal of this study is to determine whether pathways involved with mitochondrial fusion or fission, are disrupted during renal CS. METHODS: Male Lewis rat kidneys were exposed to cold storage (CS) alone or cold storage combined with transplantation (CS/Tx)...
2017: PloS One
https://www.readbyqxmd.com/read/28944836/aberrant-promoter-methylation-of-multiple-genes-in-vsmc-proliferation-induced-by-hcy
#10
Sheng-Chao Ma, Jian-Cheng Cao, Hui-Ping Zhang, Yun Jiao, Hui Zhang, Yang-Yang He, Yan-Hua Wang, Xiao-Ling Yang, An-Ning Yang, Jue Tian, Ming-Hao Zhang, Xiao-Ming Yang, Guan-Jun Lu, Shao-Ju Jin, Yue-Xia Jia, Yi-Deng Jiang
Vascular smooth muscle cell (VSMC) proliferation is a primary pathological event in atherosclerosis (AS), and homocysteine (Hcy) is an independent risk factor for AS. However, the underlying mechanisms are still lagging. Studies have used the combination of methylation of promoters of multiple genes to diagnose tumors, thus the aim of the current study was to investigate the role of methylation status of several genes in VSMCs treated with Hcy. CpG islands were identified in the promoters of platelet‑derived growth factor (PDGF), p53, phosphatase and tensin homologue on chromosome 10 (PTEN) and mitofusin 2 (MFN2)...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28944094/the-arl2-gtpase-regulates-mitochondrial-fusion-from-the-intermembrane-space
#11
Laura E Newman, Cara R Schiavon, Rachel E Turn, Richard A Kahn
Mitochondria are essential, dynamic organelles that regularly undergo both fusion and fission in response to cellular conditions, though mechanisms of the regulation of their dynamics are incompletely understood. We provide evidence that increased activity of the small GTPase ARL2 is strongly correlated with an increase in fusion, while loss of ARL2 activity results in a decreased rate of mitochondrial fusion. Strikingly, expression of activated ARL2 can partially restore the loss of fusion resulting from deletion of either mitofusin 1 (MFN1) or mitofusin 2 (MFN2), but not deletion of both...
2017: Cellular Logistics
https://www.readbyqxmd.com/read/28943312/ubiquitin-linkage-specific-affimers-reveal-insights-into-k6-linked-ubiquitin-signaling
#12
Martin A Michel, Kirby N Swatek, Manuela K Hospenthal, David Komander
Several ubiquitin chain types have remained unstudied, mainly because tools and techniques to detect these posttranslational modifications are scarce. Linkage-specific antibodies have shaped our understanding of the roles and dynamics of polyubiquitin signals but are available for only five out of eight linkage types. We here characterize K6- and K33-linkage-specific "affimer" reagents as high-affinity ubiquitin interactors. Crystal structures of affimers bound to their cognate chain types reveal mechanisms of specificity and a K11 cross-reactivity in the K33 affimer...
October 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28939434/inhibition-of-drp1-mediated-mitochondrial-fission-improves-mitochondrial-dynamics-and-bioenergetics-stimulating-neurogenesis-in-hippocampal-progenitor-cells-from-a-down-syndrome-mouse-model
#13
Daniela Valenti, Leonardo Rossi, Domenico Marzulli, Francesco Bellomo, Domenico De Rasmo, Anna Signorile, Rosa Anna Vacca
Functional and structural damages to mitochondria have been critically associated with the pathogenesis of Down syndrome (DS), a human multifactorial disease caused by trisomy of chromosome 21 and associated with neurodevelopmental delay, intellectual disability and early neurodegeneration. Recently, we demonstrated in neural progenitor cells (NPCs) isolated from the hippocampus of Ts65Dn mice -a widely used model of DS - a severe impairment of mitochondrial bioenergetics and biogenesis and reduced NPC proliferation...
September 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28924745/hypertonia-linked-protein-trak1-functions-with-mitofusins-to-promote-mitochondrial-tethering-and-fusion
#14
Crystal A Lee, Lih-Shen Chin, Lian Li
Hypertonia is a neurological dysfunction associated with a number of central nervous system disorders, including cerebral palsy, Parkinson's disease, dystonia, and epilepsy. Genetic studies have identified a homozygous truncation mutation in Trak1 that causes hypertonia in mice. Moreover, elevated Trak1 protein expression is associated with several types of cancers and variants in Trak1 are linked to childhood absence epilepsy in humans. Despite the importance of Trak1 in health and disease, the mechanisms of Trak1 action remain unclear and the pathogenic effects of Trak1 mutation are unknown...
September 18, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28923829/estrogen-deprivation-aggravates-cardiac-hypertrophy-in-nonobese-type-2-diabetic-goto-kakizaki-gk-rats
#15
Nattayaporn Apaijai, Narattaphol Charoenphandhu, Jitjiroj Ittichaichareon, Panan Suntornsaratoon, Nateetip Krishnamra, Ratchaneevan Aeimlapa, Siriporn C Chattipakorn, Nipon Chattipakorn
Both Type 2 diabetes mellitus (T2DM) and estrogen deprivation have been shown to be associated with the development of cardiovascular disease and adverse cardiac remodeling. However, the role of estrogen deprivation on adverse cardiac remodeling in nonobese T2DM rats has not been clearly elucidated. We hypothesized that estrogen-deprivation aggravates adverse cardiac remodeling in Goto-Kakizaki (GK) rats. Wild-type (WT) and GK rats at the age of 9 months old were divided into two subgroups to have either a sham operation (WTS, GKS) or a bilateral ovariectomy (WTO, GKO) (n = 6/subgroup)...
October 31, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28911913/phosphatidic-acid-and-cardiolipin-coordinate-mitochondrial-dynamics
#16
REVIEW
Shoichiro Kameoka, Yoshihiro Adachi, Koji Okamoto, Miho Iijima, Hiromi Sesaki
Membrane organelles comprise both proteins and lipids. Remodeling of these membrane structures is controlled by interactions between specific proteins and lipids. Mitochondrial structure and function depend on regulated fusion and the division of both the outer and inner membranes. Here we discuss recent advances in the regulation of mitochondrial dynamics by two critical phospholipids, phosphatidic acid (PA) and cardiolipin (CL). These two lipids interact with the core components of mitochondrial fusion and division (Opa1, mitofusin, and Drp1) to activate and inhibit these dynamin-related GTPases...
September 11, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28904083/assessing-the-effects-of-mitofusin-2-deficiency-in-the-adult-heart-using-3d-electron-tomography
#17
Siavash Beikoghli Kalkhoran, Andrew R Hall, Ian J White, Jackie Cooper, Qiao Fan, Sang-Bing Ong, Sauri Hernández-Reséndiz, Hector Cabrera-Fuentes, Kroekkiat Chinda, Bibhas Chakraborty, Gerald W Dorn, Derek M Yellon, Derek J Hausenloy
The effects of mitofusin 2 (MFN2) deficiency, on mitochondrial morphology and the mitochondria-junctional sarcoplasmic reticulum (jSR) complex in the adult heart, have been previously investigated using 2D electron microscopy, an approach which is unable to provide a 3D spatial assessment of these imaging parameters. Here, we use 3D electron tomography to show that MFN2-deficient mitochondria are larger in volume, more elongated, and less rounded; have fewer mitochondria-jSR contacts, and an increase in the distance between mitochondria and jSR, when compared to WT mitochondria...
September 2017: Physiological Reports
https://www.readbyqxmd.com/read/28881757/antagonistic-effects-of-selenium-on-cadmium-induced-apoptosis-by-restoring-the-mitochondrial-dynamic-equilibrium-and-energy-metabolism-in-chicken-spleens
#18
Zhe Xu, Xi Jin, Tingru Pan, Tianqi Liu, Na Wan, Shu Li
The aim of this study was to investigate the mechanism of cadmium-induced apoptosis in chicken spleens and the antagonistic effects of selenium. We duplicated the selenium-cadmium interaction model and examined the expression of apoptosis-, immune-, mitochondrial dynamics- and energy metabolism-related genes. The results demonstrated that after treatment with cadmium, the frequency of apoptosis was significantly increased, and the morphological characteristics of apoptosis were observed. The expression of pro-apoptotic genes was increased, and that of anti-apoptotic genes was decreased...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28860650/a-membrane-inserted-structural-model-of-the-yeast-mitofusin-fzo1
#19
Dario De Vecchis, Laetitia Cavellini, Marc Baaden, Jérôme Hénin, Mickaël M Cohen, Antoine Taly
Mitofusins are large transmembrane GTPases of the dynamin-related protein family, and are required for the tethering and fusion of mitochondrial outer membranes. Their full-length structures remain unknown, which is a limiting factor in the study of outer membrane fusion. We investigated the structure and dynamics of the yeast mitofusin Fzo1 through a hybrid computational and experimental approach, combining molecular modelling and all-atom molecular dynamics simulations in a lipid bilayer with site-directed mutagenesis and in vivo functional assays...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28859443/imbalance-in-mitochondrial-dynamics-and-apoptosis-in-pregnancies-among-hiv-infected-women-on-haart-with-obstetric-complications
#20
Mariona Guitart-Mampel, A Sandra Hernandez, Constanza Moren, Marc Catalan-Garcia, Ester Tobias, Ingrid Gonzalez-Casacuberta, Diana L Juarez-Flores, Josep M Gatell, Francesc Cardellach, Jose C Milisenda, Josep M Grau, Eduard Gratacos, Francesc Figueras, Gloria Garrabou
Background: HIV infection and HAART trigger genetic and functional mitochondrial alterations leading to cell death and adverse clinical manifestations. Mitochondrial dynamics enable mitochondrial turnover and degradation of damaged mitochondria, which may lead to apoptosis. Objectives: To evaluate markers of mitochondrial dynamics and apoptosis in pregnancies among HIV-infected women on HAART and determine their potential association with obstetric complications...
September 1, 2017: Journal of Antimicrobial Chemotherapy
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