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https://www.readbyqxmd.com/read/28314909/localization-of-dynamin-related-protein-1-and-its-potential-role-in-lamellipodia-formation
#1
Youhwa Jo, Hyo Min Cho, Woong Sun, Jae Ryun Ryu
Dynamin-related protein1 (Drp1) plays an essential role in mitochondrial fission: Cytosolic Drp1 is translocated to the mitochondria upon stimulus, and oligomerized Drp1 constricts mitochondria by aid of actin filaments. Drp1 completes the fission process with GTP hydrolysis by its own GTPase activity. The importance of actin filament and its interaction with Drp1 in the mitochondrial fission process have been demonstrated. In this study, we found that Drp1 is enriched in the actin-rich leading edge of lamellipodia of mouse embryonic fibroblasts (MEFs) wherein mitochondria or peroxisomes are absent...
March 17, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28302704/swimming-attenuates-d-galactose-induced-brain-aging-via-suppressing-mir-34a-mediated-autophagy-impairment-and-abnormal-mitochondrial-dynamics
#2
Xianjuan Kou, Jie Li, Xingran Liu, Jingru Chang, Qingxia Zhao, Shaohui Jia, Jingjing Fan, Ning Chen
MicroRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. In order to explore the regulatory role of miR-34a in aging-related diseases such as Alzheimer's disease (AD) during exercise intervention, we constructed a rat model with (D-galactose) D-gal-induced oxidative stress and cognitive impairment coupled with dysfunctional autophagy and abnormal mitochondrial dynamics, determined the mitigation of cognitive impairment of D-gal-induced aging rats during swimming intervention, and evaluated miR-34a-mediated functional status of autophagy and abnormal mitochondrial dynamics...
March 16, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28302504/mitochondrial-nudix-hydrolases-a-metabolic-link-between-nad-catabolism-gtp-and-mitochondrial-dynamics
#3
Aaron Long, Nina Klimova, Tibor Kristian
NAD(+) catabolism and mitochondrial dynamics are important parts of normal mitochondrial function and are both reported to be disrupted in aging, neurodegenerative diseases, and acute brain injury. While both processes have been extensively studied there has been little reported on how the mechanisms of these two processes are linked. This review focuses on how downstream NAD(+) catabolism via NUDIX hydrolases affects mitochondrial dynamics under pathologic conditions. Additionally, several potential targets in mitochondrial dysfunction and fragmentation are discussed, including the roles of mitochondrial poly(ADP-ribose) polymerase 1(mtPARP1), AMPK, AMP, and intra-mitochondrial GTP metabolism...
March 14, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28283188/targeted-cytoplasmic-irradiation-and-autophagy
#4
Jinhua Wu, Bo Zhang, Yen-Ruh Wuu, Mercy M Davidson, Tom K Hei
The effect of ionizing irradiation on cytoplasmic organelles is often underestimated because the general dogma considers direct DNA damage in the nuclei to be the primary cause of radiation induced toxicity. Using a precision microbeam irradiator, we examined the changes in mitochondrial dynamics and functions triggered by targeted cytoplasmic irradiation with α-particles. Mitochondrial dysfunction induced by targeted cytoplasmic irradiation led to activation of autophagy, which degraded dysfunctional mitochondria in order to maintain cellular energy homeostasis...
March 1, 2017: Mutation Research
https://www.readbyqxmd.com/read/28282614/inhibition-of-drp1-protects-against-senecionine-induced-mitochondria-mediated-apoptosis-in-primary-hepatocytes-and-in-mice
#5
Xiao Yang, Hua Wang, Hong-Min Ni, Aizhen Xiong, Zhengtao Wang, Hiromi Sesaki, Wen-Xing Ding, Li Yang
Pyrrolizidine alkaloids (PAs) are a group of compounds found in various plants and some of them are widely consumed in the world as herbal medicines and food supplements. PAs are potent hepatotoxins that cause irreversible liver injury in animals and humans. However, the mechanisms by which PAs induce liver injury are not clear. In the present study, we determined the hepatotoxicity and molecular mechanisms of senecionine, one of the most common toxic PAs, in primary cultured mouse and human hepatocytes as well as in mice...
March 2, 2017: Redox Biology
https://www.readbyqxmd.com/read/28273447/dynamin-related-protein-1-dependent-mitochondrial-fission-changes-in-the-dorsal-vagal-complex-regulate-insulin-action
#6
Beatrice M Filippi, Mona A Abraham, Pamuditha N Silva, Mozhgan Rasti, Mary P LaPierre, Paige V Bauer, Jonathan V Rocheleau, Tony K T Lam
Mitochondria undergo dynamic changes to maintain function in eukaryotic cells. Insulin action in parallel regulates glucose homeostasis, but whether specific changes in mitochondrial dynamics alter insulin action and glucose homeostasis remains elusive. Here, we report that high-fat feeding in rodents incurred adaptive dynamic changes in mitochondria through an increase in mitochondrial fission in parallel to an activation of dynamin-related protein 1 (Drp1) in the dorsal vagal complex (DVC) of the brain. Direct inhibition of Drp1 negated high-fat-feeding-induced mitochondrial fission, endoplasmic reticulum (ER) stress, and insulin resistance in the DVC and subsequently restored hepatic glucose production regulation...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28272266/lack-of-activation-of-mitophagy-during-endurance-exercise-in-human
#7
Céline Schwalm, Louise Deldicque, Marc Francaux
PURPOSE: To determine whether fission and mitophagy are activated by acute endurance exercise in human skeletal muscle and to investigate if this activation is dependent upon the nutritional state. METHODS: Trained athletes (n = 7) cycled for 2 h at 70% VO2 peak in a fed or fasted state. Vastus lateralis muscle biopsies were obtained at baseline, before, immediately after and 1 h after exercise. Protein and mRNA markers for mitophagy, mitochondrial biogenesis, fission and fusion were analyzed using qRT-PCR and Western blot...
March 8, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28266127/mitochondrial-pkc-%C3%AE%C2%B5-deficiency-promotes-i-r-mediated-myocardial-injury-via-gsk3%C3%AE-dependent-mitochondrial-permeability-transition-pore-opening
#8
Shijun Wang, Feng Zhang, Gang Zhao, Yong Cheng, Ting Wu, Bing Wu, You-En Zhang
Mitochondrial fission is critically involved in cardiomyocyte apoptosis, which has been considered as one of the leading causes of ischaemia/reperfusion (I/R)-induced myocardial injury. In our previous works, we demonstrate that aldehyde dehydrogenase-2 (ALDH2) deficiency aggravates cardiomyocyte apoptosis and cardiac dysfunction. The aim of this study was to elucidate whether ALDH2 deficiency promotes mitochondrial injury and cardiomyocyte death in response to I/R stress and the underlying mechanism. I/R injury was induced by aortic cross-clamping for 45 min...
March 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28265681/ischemia-induced-drp1-and-fis1-mediated-mitochondrial-fission-and-right-ventricular-dysfunction-in-pulmonary-hypertension
#9
Lian Tian, Monica Neuber-Hess, Jeffrey Mewburn, Asish Dasgupta, Kimberly Dunham-Snary, Danchen Wu, Kuang-Hueih Chen, Zhigang Hong, Willard W Sharp, Shelby Kutty, Stephen L Archer
Right ventricular (RV) function determines prognosis in pulmonary arterial hypertension (PAH). We hypothesize that ischemia causes RV dysfunction in PAH by triggering dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. RV function was compared in control rats (n = 50) versus rats with monocrotaline-induced PAH (MCT-PAH; n = 60) both in vivo (echocardiography) and ex vivo (RV Langendorff). Mitochondrial membrane potential and morphology and RV function were assessed before or after 2 cycles of ischemia-reperfusion injury challenge (RV-IR)...
March 6, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28262828/senp3-mediated-desumoylation-of-drp1-facilitates-interaction-with-mff-to-promote-cell-death
#10
Chun Guo, Kevin A Wilkinson, Ashley J Evans, Philip P Rubin, Jeremy M Henley
The GTPase dynamin-related protein 1 (Drp1) is essential for physiological and pathophysiological mitochondrial fission. DeSUMOylation of Drp1 by the enzyme SENP3 promotes cell death during reperfusion after ischaemia by enhancing Drp1 partitioning to the mitochondrial outer membrane (MOM), which causes cytochrome c release and apoptosis. However, how deSUMOylation recruits Drp1 to the MOM is unknown. Here we show that deSUMOylation selectively promotes Drp1 binding to the MOM resident adaptor protein mitochondrial fission factor (Mff)...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28260920/tbx2-confers-poor-prognosis-in-glioblastoma-and-promotes-temozolomide-resistance-with-change-of-mitochondrial-dynamics
#11
Fuxin Yi, Jianzhou Du, Weimin Ni, Weixian Liu
Tbx2 is a cancer-related protein that was found to be overexpressed in several human malignancies. The present study aims to investigate the clinical significance and biological role of Tbx2 in human astrocytoma. We examined its protein expression in 102 cases of astrocytoma tissues using immunohistochemical staining. Negative Tbx2 staining was observed in normal astrocytes, and positive nuclear staining was found in 41 out of 102 astrocytoma specimens. The rate of Tbx2 overexpression in pylocytic astrocytoma, diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma multiform (GBM) were 0%, 26...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28242326/therapeutic-hypothermia-attenuates-global-cerebral-reperfusion-induced-mitochondrial-damage-by-suppressing-dynamin-related-protein-1-activation-and-mitochondria-mediated-apoptosis-in-a-cardiac-arrest-rat-model
#12
Jingjing Fan, Shenquan Cai, Hao Zhong, Liangbin Cao, Kangli Hui, Miaomiao Xu, Manlin Duan, Jianguo Xu
Therapeutic hypothermia is effective to attenuate brain ischemia/reperfusion (I/R) injury after cardiac arrest, and multiple mechanisms have been proposed. Dynamin-related protein 1 (Drp1), a large GTPases of dynamin superfamily, predominantly controls mitochondrial fission and is related to IR-induced Cyt C release and apoptosis. However, the effect of therapeutic hypothermia on Drp1 and mitochondrial fission after cardiac arrest remains still unclear. In this study, non-cardiac arrest and post-cardiac arrest rats received 6-h normothermia (37-38°C) or therapeutic hypothermia (32-34°C), and the hippocampus was harvested at 6h and 72h after cardiac arrest...
February 24, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28238968/changes-in-macroautophagy-chaperone-mediated-autophagy-and-mitochondrial-metabolism-in-murine-skeletal-and-cardiac-muscle-during-aging
#13
Jin Zhou, Shu Yun Chong, Andrea Lim, Brijesh K Singh, Rohit A Sinha, Adam B Salmon, Paul M Yen
Aging causes a general decline in cellular metabolic activity, and function in different tissues and whole body homeostasis. However, the understanding about the metabolomic and autophagy changes in skeletal muscle and heart during aging is still limited. We thus examined markers for macroautophagy, chaperone-mediated autophagy (CMA), mitochondrial quality control, as well as cellular metabolites in skeletal and cardiac muscle from young (5 months old) and aged (27 months old) mice. We found decreased autophagic degradation of p62 and increased ubiquitinated proteins in both tissues from aged mice, suggesting a decline in macroautophagy during aging...
February 26, 2017: Aging
https://www.readbyqxmd.com/read/28238799/inhibition-of-drp1-hyper-activation-is-protective-in-animal-models-of-experimental-multiple-sclerosis
#14
Fucheng Luo, Karl Herrup, Xin Qi, Yan Yang
Multiple Sclerosis (MS), a leading neurological disorder of young adults, is characterized by the loss of oligodendrocytes (OLs), demyelination, inflammation and neuronal degeneration. Here we show that dynamin-related protein 1 (Drp1), a mitochondrial fission protein, is activated in primary OL cells exposed to TNF-α induced inflammation or oxidative stress, as well as in EAE-immunized and cuprizone toxicity-induced demyelinating mouse models. Inhibition of Drp1 hyper-activation by the selective inhibitor P110 abolishes Drp1 translocation to the mitochondria, reduces mitochondrial fragmentation and stems necrosis in primary OLs exposed to TNF-α and H2O2...
February 24, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28230856/ginsenoside-rg5-increases-cardiomyocyte-resistance-to-ischemic-injury-through-regulation-of-mitochondrial-hexokinase-ii-and-dynamin-related-protein-1
#15
Yi-Lin Yang, Jia Li, Kang Liu, Lei Zhang, Qun Liu, Baolin Liu, Lian-Wen Qi
Hexokinase-II (HK-II) and dynamin-related protein 1 (Drp1) regulate mitochondrial function differently. This study was designed to investigate the cardioprotective effect of ginsenoside Rg5 (Rg5) with emphasis on the regulation of mitochondrial HK-II and Drp1. Saturated acid palmitate (PA) stimulation increased lactate accumulation and induced cellular acidification by impairing the activity of pyruvate dehydrogenase (PDH) in cardiomyocytes, leading to HK-II dissociation from mitochondria. Rg5 improved PDH activity and prevented cellular acidification by combating fatty-acid oxidation, contributing to protecting mitochondrial HK-II...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28224980/alpha-synuclein-prevents-the-formation-of-spherical-mitochondria-and-apoptosis-under-oxidative-stress
#16
Stefanie Menges, Georgia Minakaki, Patrick M Schaefer, Holger Meixner, Iryna Prots, Ursula Schlötzer-Schrehardt, Kristina Friedland, Beate Winner, Tiago F Outeiro, Konstanze F Winklhofer, Christine A F von Arnim, Wei Xiang, Jürgen Winkler, Jochen Klucken
Oxidative stress (OS), mitochondrial dysfunction, and dysregulation of alpha-synuclein (aSyn) homeostasis are key pathogenic factors in Parkinson's disease. Nevertheless, the role of aSyn in mitochondrial physiology remains elusive. Thus, we addressed the impact of aSyn specifically on mitochondrial response to OS in neural cells. We characterize a distinct type of mitochondrial fragmentation, following H2O2 or 6-OHDA-induced OS, defined by spherically-shaped and hyperpolarized mitochondria, termed "mitospheres"...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28213011/calorie-restriction-promotes-cardiolipin-biosynthesis-and-distribution-between-mitochondrial-membranes
#17
Luis Alberto Luévano-Martínez, Maria Fernanda Forni, Julia Peloggia, Ii-Sei Watanabe, Alicia J Kowaltowski
Calorie restriction (CR) has been amply demonstrated to modify mitochondrial function. However, little is known regarding the effects of this dietary regimen on mitochondrial membranes. We isolated phospholipids from rat liver mitochondria from animals on CR or ad libitum diets and found that mitochondria from ad libitum animals present an increased content of lipoperoxides and the content of cardiolipin. Cardiolipin is the main anionic phospholipid present in mitochondrial membranes, and plays a key role in mitochondrial function, signaling and stress response...
February 14, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28210956/mdivi-1-alleviates-early-brain-injury-after-experimental-subarachnoid-hemorrhage-in-rats-possibly-via-inhibition-of-drp1-activated-mitochondrial-fission-and-oxidative-stress
#18
Pei Wu, Yuchen Li, Shiyi Zhu, Chunlei Wang, Jiaxing Dai, Guang Zhang, Bingjie Zheng, Shancai Xu, Ligang Wang, Tongyu Zhang, PeiQuan Zhou, John H Zhang, Huaizhang Shi
Mdivi-1 is a selective inhibitor of mitochondrial fission protein, Drp1, and can penetrate the blood-brain barrier. Previous studies have shown that Mdivi-1 improves neurological outcomes after ischemia, seizures and trauma but it remains unclear whether Mdivi-1 can attenuate early brain injury after subarachnoid hemorrhage (SAH). We thus investigated the therapeutic effect of Mdivi-1 on early brain injury following SAH. Rats were randomly divided into four groups: sham; SAH; SAH + vehicle; and SAH + Mdivi-1...
February 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28207880/skeletal-muscle-metabolic-adaptations-to-endurance-exercise-training-are-attainable-in-mice-with-simvastatin-treatment
#19
William M Southern, Anna S Nichenko, Daniel D Shill, Corey C Spencer, Nathan T Jenkins, Kevin K McCully, Jarrod A Call
We tested the hypothesis that a 6-week regimen of simvastatin would attenuate skeletal muscle adaptation to low-intensity exercise. Male C57BL/6J wildtype mice were subjected to 6-weeks of voluntary wheel running or normal cage activities with or without simvastatin treatment (20 mg/kg/d, n = 7-8 per group). Adaptations in in vivo fatigue resistance were determined by a treadmill running test, and by ankle plantarflexor contractile assessment. The tibialis anterior, gastrocnemius, and plantaris muscles were evaluated for exercised-induced mitochondrial adaptations (i...
2017: PloS One
https://www.readbyqxmd.com/read/28202127/-role-of-mitophagy-in-neonatal-rats-with-hypoxic-ischemic-brain-damage
#20
Ming-Xi Li, Yi Qu, De-Zhi Mu
OBJECTIVE: To investigate mitophagy in an animal model of hypoxic-ischemic brain damage (HIBD) and its role in HIBD. METHODS: A total of 120 neonatal Sprague-Dawley rats aged 7 days were divided into three groups: sham-operation, HIBD, and autophagy inhibitor intervention (3MA group). The rats in the HIBD group were treated with right common carotid artery ligation and then put in a hypoxic chamber (8% oxygen and 92% nitrogen) for 2.5 hours. Those in the 3MA group were given ligation and hypoxic treatment at 30 minutes after intraperitoneal injection of 2 μL 3MA...
February 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
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