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https://www.readbyqxmd.com/read/27920125/structures-of-human-mitofusin-1-provide-insight-into-mitochondrial-tethering
#1
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/27907123/mice-hemizygous-for-a-pathogenic-mitofusin-2-allele-exhibit-hind-limb-foot-gait-deficits-and-phenotypic-perturbations-in-nerve-and-muscle
#2
Peter Bannerman, Travis Burns, Jie Xu, Laird Miers, David Pleasure
Charcot-Marie-Tooth disease type 2A (CMT2A), the most common axonal form of hereditary sensory motor neuropathy, is caused by mutations of mitofusin-2 (MFN2). Mitofusin-2 is a GTPase required for fusion of mitochondrial outer membranes, repair of damaged mitochondria, efficient mitochondrial energetics, regulation of mitochondrial-endoplasmic reticulum calcium coupling and axonal transport of mitochondria. We knocked T105M MFN2 preceded by a loxP-flanked STOP sequence into the mouse Rosa26 locus to permit cell type-specific expression of this pathogenic allele...
2016: PloS One
https://www.readbyqxmd.com/read/27895764/mitofusin-2-prevents-skeletal-muscle-wasting-in-cancer-cachexia
#3
Qiu-Lei Xi, Bo Zhang, Yi Jiang, Hai-Sheng Zhang, Qing-Yang Meng, Ying Chen, Yu-Song Han, Qiu-Lin Zhuang, Jun Han, Hai-Yu Wang, Jing Fang, Guo-Hao Wu
Cancer cachexia remains a leading cause of morbidity and mortality worldwide, despite extensive research and clinical trials. The prominent clinical feature of cancer cachexia is the continuous loss of skeletal muscle that cannot be fully reversed by conventional nutritional support, and that leads to progressive functional impairment. The mechanism underlying muscle loss in patients with cachexia is poorly understood. The present study analyzed 21 cancer patients with or without cachexia, and demonstrated that mitofusin-2 (Mfn2) was downregulated in the rectus abdominis of patients with cachexia, which was associated with body weight loss...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27889468/mitochondrial-cristae-remodelling-is-associated-with-disrupted-opa1-oligomerisation-in-the-huntington-s-disease-r6-2-fragment-model
#4
Tanja Hering, Kerstin Kojer, Nathalie Birth, Jaqueline Hallitsch, Jan-Willem Taanman, Michael Orth
There is evidence of an imbalance of mitochondrial fission and fusion in patients with Huntington's disease (HD) and HD animal models. Fission and fusion are important for mitochondrial homeostasis including mitochondrial DNA (mtDNA) maintenance and may be relevant for the selective striatal mtDNA depletion that we observed in the R6/2 fragment HD mouse model. We aimed to investigate the fission/fusion balance and the integrity of the mitochondrial membrane system in cortex and striatum of end-stage R6/2 mice and wild-type animals...
November 23, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27881711/mitochondrial-fusion-reaching-the-end-of-mitofusin-s-tether
#5
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/27873387/physical-exercise-remodels-visceral-adipose-tissue-and-mitochondrial-lipid-metabolism-in-rats-fed-a-high-fat-diet
#6
Sílvia Rocha-Rodrigues, Amaia Rodríguez, Sara Becerril, Beatriz Ramírez, I O Gonçalves, Jorge Beleza, Gema Frühbeck, António Ascensão, José Magalhães
We aimed to investigate the effects of two physical exercise models, voluntary physical activity (VPA) and endurance training (ET) as preventive and therapeutic strategies, respectively, on lipid accumulation regulators and mitochondrial content in VAT of rats fed a high-fat diet (HFD). Sprague Dawley rats (6 wks old, n=60) were assigned into sedentary and VPA groups fed isoenergetic diets: standard (S, 35 kcal% fat) or HFD (71 kcal% fat). The VPA groups had free access to wheel running during the entire protocol...
November 22, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27861739/afzelin-ameliorates-d-galactosamine-and-lipopolysaccharide-induced-fulminant-hepatic-failure-by-modulating-mitochondrial-quality-control-and-dynamics-150-150
#7
Sang-Bin Lee, Jung-Woo Kang, So-Jin Kim, Jongmin Ahn, Jinwoong Kim, Sun-Mee Lee
BACKGROUND AND PURPOSE: Fulminant hepatic failure (FHF) is a fatal clinical syndrome that results in excessive inflammation and hepatocyte death. Mitochondrial dysfunction is considered to be a possible mechanism of FHF. Afzelin, a flavonol glycoside found in Houttuynia cordata Thunberg, has anti-inflammatory and antioxidant properties. The present study elucidated the cytoprotective mechanisms of afzelin against D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced FHF, particularly focusing on mitochondrial quality control and dynamics...
November 15, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27847330/altered-mitochondrial-quality-control-signaling-in-muscle-of-old-gastric-cancer-patients-with-cachexia
#8
Emanuele Marzetti, Maria Lorenzi, Francesco Landi, Anna Picca, Fausto Rosa, Fabiana Tanganelli, Marco Galli, Giovanni Battista Doglietto, Fabio Pacelli, Matteo Cesari, Roberto Bernabei, Riccardo Calvani, Maurizio Bossola
Mitochondrial dysfunction is involved in the loss of muscle featuring both aging and cancer cachexia (CC). Whether mitochondrial quality control (MQC) is altered in skeletal myocytes of old patients with CC is unclear. The present investigation therefore sought to preliminarily characterize MQC pathways in muscle of old gastric cancer patients with cachexia. The study followed a case-control cross-sectional design. Intraoperative biopsies of the rectus abdominis muscle were obtained from 18 patients with gastric adenocarcinoma (nine with CC and nine non-cachectic) and nine controls, and assayed for the expression of a set of MQC mediators...
November 12, 2016: Experimental Gerontology
https://www.readbyqxmd.com/read/27844171/mitochondrial-dynamics-as-a-therapeutic-target-for-treating-cardiac-diseases
#9
Sang-Bing Ong, Derek J Hausenloy
Mitochondria are dynamic in nature and are able to shift their morphology between elongated interconnected mitochondrial networks and a fragmented disconnected arrangement by the processes of mitochondrial fusion and fission, respectively. Changes in mitochondrial morphology are regulated by the mitochondrial fusion proteins - mitofusins 1 and 2 (Mfn1 and 2), and optic atrophy 1 (Opa1) as well as the mitochondrial fission proteins - dynamin-related peptide 1 (Drp1) and fission protein 1 (Fis1). Despite having a unique spatial arrangement, cardiac mitochondria have been implicated in a variety of disorders including ischemia-reperfusion injury (IRI), heart failure, diabetes, and pulmonary hypertension...
November 15, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27832814/obesity-induced-cardiac-lipid-accumulation-in-adult-mice-is-modulated-by-g-protein-coupled-receptor-kinase-2-levels
#10
Elisa Lucas, Rocio Vila-Bedmar, Alba C Arcones, Marta Cruces-Sande, Victoria Cachofeiro, Federico Mayor, Cristina Murga
BACKGROUND: The leading cause of death among the obese population is heart failure and stroke prompted by structural and functional changes in the heart. The molecular mechanisms that underlie obesity-related cardiac remodeling are complex, and include hemodynamic and metabolic alterations that ultimately affect the functionality of the myocardium. G protein-coupled receptor kinase 2 (GRK2) is an ubiquitous kinase able to desensitize the active form of several G protein-coupled receptors (GPCR) and is known to play an important role in cardiac GPCR modulation...
November 10, 2016: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/27830717/effect-of-heme-oxygenase-1-on-mitofusin-1-protein-in-lps-induced-ali-ards-in-rats
#11
Jianbo Yu, Ying Wang, Zhen Li, Shuan Dong, Dan Wang, Lirong Gong, Jia Shi, Yuan Zhang, Daquan Liu, Rui Mu
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common and important oxidative stress in the lung. Mitochondrial fusion responds to the normal morphology and function of cells and is finely regulated by mitochondrial fusion proteins, such as mitofusin-1 protein (Mfn1), mitofusin-2 protein (Mfn2) and optical atrophy 1 (OPA1). Additionally, Mfn1 has been identified as the most important protein in mitochondrial fusion. Heme oxygenase-1 (HO-1) is a stress-inducible protein that plays a critical role in protecting against oxidative stress...
November 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27807421/cancer-and-chemotherapy-contribute-to-muscle-loss-by-activating-common-signaling-pathways
#12
Rafael Barreto, Giorgia Mandili, Frank A Witzmann, Francesco Novelli, Teresa A Zimmers, Andrea Bonetto
Cachexia represents one of the primary complications of colorectal cancer due to its effects on depletion of muscle and fat. Evidence suggests that chemotherapeutic regimens, such as Folfiri, contribute to cachexia-related symptoms. The purpose of the present study was to investigate the cachexia signature in different conditions associated with severe muscle wasting, namely Colon-26 (C26) and Folfiri-associated cachexia. Using a quantitative LC-MS/MS approach, we identified significant changes in 386 proteins in the quadriceps muscle of Folfiri-treated mice, and 269 proteins differentially expressed in the C26 hosts (p < 0...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27801955/curcumin-prevents-mitochondrial-dynamics-disturbances-in-early-5-6-nephrectomy-relation-to-oxidative-stress-and-mitochondrial-bioenergetics
#13
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...
November 1, 2016: BioFactors
https://www.readbyqxmd.com/read/27794519/a-novel-fission-independent-role-of-dynamin-related-protein-1-in-cardiac-mitochondrial-respiration
#14
Huiliang Zhang, Pei Wang, Sara Bisetto, Yisang Yoon, Quan Chen, Shey-Shing Sheu, Wang Wang
AIMS: Mitochondria in adult cardiomyocytes exhibit static morphology and infrequent dynamic changes, despite the high abundance of fission and fusion regulatory proteins in the heart. Previous reports have indicated that fusion proteins may bear functions beyond morphology regulation. Here, we investigated the role of fission protein, dynamin-related protein 1 (DRP1), on mitochondrial respiration regulation in adult cardiomyocytes. METHODS AND RESULTS: By using genetic or pharmacological approaches, we manipulated the activity or protein level of fission and fusion proteins and found they mildly influenced mitochondrial morphology in adult rodent cardiomyocytes, which is in contrast to their significant effect in H9C2 cardiac myoblasts...
October 29, 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/27776427/phyllanthus-urinaria-s-inhibition-of-human-osteosarcoma-xenografts-growth-in-mice-is-associated-with-modulation-of-mitochondrial-fission-fusion-machinery
#15
Sheng-Teng Huang, Chao-Chun Huang, Jer-Ming Sheen, Tsu-Kung Lin, Pei-Lin Liao, Wen-Liang Huang, Pei-Wen Wang, Chia-Wei Liou, Jiin-Haur Chuang
Osteosarcoma is an aggressive bone cancer arising from primitive transformed cells of mesenchymal origin to form malignant osteoid. Phyllanthus urinaria [Formula: see text]P. urinaria[Formula: see text] is a widely used folk medicine in cancer treatment, however the mechanism of P. urinaria inhibited human osteosarcoma is unclear. The present study was aimed at investigating the antitumoral effects of an aqueous P. urinaria on human osteosarcoma in vivo and the related underlying mechanisms, mainly focusing on mitochondrial dynamic dysfunction...
2016: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/27775718/correcting-mitochondrial-fusion-by-manipulating-mitofusin-conformations
#16
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 Ii
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/27731374/exercise-training-alleviates-hypoxia-induced-mitochondrial-dysfunction-in-the-lymphocytes-of-sedentary-males
#17
Hsing-Hua Tsai, Shao-Chiang Chang, Cheng-Hsien Chou, Tzu-Pin Weng, Chih-Chin Hsu, Jong-Shyan Wang
This study elucidates how interval and continuous exercise regimens affect the mitochondrial functionality of lymphocytes under hypoxic stress. Sixty healthy sedentary males were randomly assigned to engage in either high-intensity interval training (HIIT, 3 min intervals at 80% and 40% VO2max, n = 20) or moderate-intensity continuous training (MICT, sustained 60% VO2max, n = 20) for 30 min/day, 5 days/week for 6 weeks or were assigned to a control group that did not receive exercise intervention (n = 20)...
October 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27706887/increased-mitochondrial-fusion-in-a-autosomal-recessive-cmt2a-family-with-mitochondrial-gtpase-mitofusin-2-mutations
#18
Philippe Codron, Arnaud Chevrollier, Mariame Selma Kane, Andoni Echaniz-Laguna, Philippe Latour, Pascal Reynier, Dominique Bonneau, Christophe Verny, Vincent Procaccio, Guy Lenaers, Julien Cassereau
Charcot-Marie-Tooth type 2A disease (CMT2A) is an inherited peripheral neuropathy mainly caused by mutations in the MFN2 gene coding for the mitochondrial fusion protein Mitofusin 2. Although the disease is mainly inherited in a dominant fashion, few cases of early-onset autosomal recessive CMT2A (AR-CMT2A) have been reported in recent years. In this study, we characterized the structure of mitochondrial network in cultured primary fibroblasts obtained from AR-CMT2A family members. The patient-derived cells showed an increase of the mitochondrial fusion with large connected networks and an increase of the mitochondrial volume...
October 5, 2016: Journal of the Peripheral Nervous System: JPNS
https://www.readbyqxmd.com/read/27698953/training-enhances-immune-cells-mitochondrial-biosynthesis-fission-fusion-and-their-antioxidant-capabilities-synergistically-with-dietary-docosahexaenoic-supplementation
#19
Carla Busquets-Cortés, Xavier Capó, Miquel Martorell, Josep A Tur, Antoni Sureda, Antoni Pons
Exercise training induces adaptations in mitochondrial metabolism, dynamics, and oxidative protection. Omega-3 fatty acids change membrane lipid composition and modulate mitochondrial function. The aim was to investigate the effect of 8-week training and docosahexaenoic acid (DHA) supplementation (1.14 g/day) on the mitochondria dynamics and antioxidant status in peripheral blood mononuclear cells (PBMCs) from sportsmen. Subjects were assigned to an intervention (N = 9) or placebo groups (N = 7) in a randomized double-blind trial...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27660309/the-role-of-drp1-adaptor-proteins-mid49-and-mid51%C3%A2-in-mitochondrial-fission-implications-for-human-disease
#20
REVIEW
Kathleen Atkins, Asish Dasgupta, Kuang-Hueih Chen, Jeff Mewburn, Stephen L Archer
Mitochondrial morphology is governed by the balance of mitochondrial fusion, mediated by mitofusins and optic atrophy 1 (OPA1), and fission, mediated by dynamin-related protein 1 (Drp1). Disordered mitochondrial dynamics alters metabolism, proliferation, apoptosis and mitophagy, contributing to human diseases, including neurodegenerative syndromes, pulmonary arterial hypertension (PAH), cancer and ischemia/reperfusion injury. Post-translational regulation of Drp1 (by phosphorylation and SUMOylation) is an established means of modulating Drp1 activation and translocation to the outer mitochondrial membrane (OMM)...
November 1, 2016: Clinical Science (1979-)
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