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https://www.readbyqxmd.com/read/29317239/protective-effect-of-mitochondrial-targeted-antioxidant-mitoq-against-iron-ion-56fe-radiation-induced-brain-injury-in-mice
#1
Lu Gan, Zhenhua Wang, Jing Si, Rong Zhou, Chao Sun, Yang Liu, Yancheng Ye, Yanshan Zhang, Zhiyuan Liu, Hong Zhang
Exposure to iron ion 56Fe radiation (IR) during space missions poses a significant risk to the central nervous system and radiation exposure is intimately linked to the production of reactive oxygen species (ROS). MitoQ is a mitochondria-targeted antioxidant that has been shown to decrease oxidative damage and lower mitochondrial ROS in a number of animal models. Therefore, the present study aimed to investigate role of the mitochondrial targeted antioxidant MitoQ against 56Fe particle irradiation-induced oxidative damage and mitochondria dysfunction in the mouse brains...
January 6, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29296759/a-specialized-pathway-for-erythroid-iron-delivery-through-lysosomal-trafficking-of-transferrin-receptor-2
#2
Shadi Khalil, Maja Holy, Stephen Grado, Robert Fleming, Ryo Kurita, Yukio Nakamura, Adam Goldfarb
Erythroid progenitors are the largest consumers of iron in the human body. In these cells, a high flux of iron must reach the mitochondrial matrix to form sufficient heme to support hemoglobinization. Canonical erythroid iron trafficking occurs via the first transferrin receptor (TfR1)-mediated endocytosis of diferric-transferrin into recycling endosomes, where ferric iron is released, reduced, and exported to the cytosol via DMT1. However, mice lacking TfR1 or DMT1 demonstrate residual erythropoiesis, suggesting additional pathways for iron use...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29290623/identification-of-new-activators-of-mitochondrial-fusion-reveals-a-link-between-mitochondrial-morphology-and-pyrimidine-metabolism
#3
Laia Miret-Casals, David Sebastián, José Brea, Eva M Rico-Leo, Manuel Palacín, Pedro M Fernández-Salguero, M Isabel Loza, Fernando Albericio, Antonio Zorzano
Mitochondria are dynamic organelles that produce most of the cellular ATP, and are involved in many other cellular functions such as Ca2+ signaling, differentiation, apoptosis, cell cycle, and cell growth. One key process of mitochondrial dynamics is mitochondrial fusion, which is catalyzed by mitofusins (MFN1 and MFN2) and OPA1. The outer mitochondrial membrane protein MFN2 plays a relevant role in the maintenance of mitochondrial metabolism, insulin signaling, and mutations that cause neurodegenerative disorders...
December 23, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29238746/determining-the-target-protein-localization-in-3d-using-the-combination-of-fib-sem-and-apex2
#4
Yang Shi, Li Wang, Jianguo Zhang, Yujia Zhai, Fei Sun
Determining the cellular localization of proteins of interest at nanometer resolution is necessary for elucidating their functions. Besides super-resolution fluorescence microscopy, conventional electron microscopy (EM) combined with immunolabeling or clonable EM tags provides a unique approach to correlate protein localization information and cellular ultrastructural information. However, there are still rare cases of such correlation in three-dimensional (3D) spaces. Here, we developed an approach by combining the focus ion beam scanning electron microscopy (FIB-SEM) and a promising clonable EM tag APEX2 (an enhanced ascorbate peroxidase 2) to determine the target protein localization within 3D cellular ultrastructural context...
2017: Biophysics Reports
https://www.readbyqxmd.com/read/29237928/correlations-between-mitofusin-2-expression-in-fibroblasts-and-pelvic-organ-prolapse-an-in-vitro-study
#5
Ye Lu, Hua-Yun Chen, Xiao-Qing Wang, Jing-Xue Wang
BACKGROUND: Both Mitofusin 2 (Mfn2) and pelvic organ prolapse (POP) are related to aging. The aim of the present study was to investigate the variations of Mfn2 expression in the uterosacral ligaments of patients with and/or without POP and their correlations with the expression of procollagen. METHODS: Fibroblasts were cultured using tissue specimens that were harvested from the uterosacral ligaments of POP and non-POP (NPOP) patients (n = 10 for each group) from September 2016 to December 2016...
December 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/29234100/a-bi-fluorescence-complementation-system-to-detect-associations-between-the-endoplasmic-reticulum-and-mitochondria
#6
Mark Harmon, Philip Larkman, Giles Hardingham, Mandy Jackson, Paul Skehel
Close contacts between the endoplasmic reticulum membrane and the mitochondrial outer membrane facilitate efficient transfer of lipids between the organelles and coordinate Ca2+ signalling and stress responses. Changes to this coupling is associated with a number of metabolic disorders and neurodegenerative diseases including Alzheimer's, Parkinson's and motor neuron disease. The distance between the two membranes at regions of close apposition is below the resolution of conventional light microscopy, which makes analysis of these interactions challenging...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29225119/d-chiro-inositol-enriched-fagopyrum-tataricum-l-gaench-extract-alleviates-mitochondrial-malfunction-and-inhibits-er-stress-jnk-associated-inflammation-in-the-endothelium
#7
Bobo Zhang, Caifeng Gao, Yunlong Li, Min Wang
ETHNOPHARMACOLOGICAL RELEVANCE: Tartary buckwheat is a food medicine dual-use crop with healing effects on cardiovascular diseases and type2 diabetes. It has been proposed that endothelial dysfunction is the initial lesion in these diseases and it's associated with mitochondrial dysfunction, endoplasmic reticulum (ER) stress and inflammation. D-chiro-inositol (DCI) is a bioactive compound of Tartary buckwheat and is always deficit in type2 diabetes. However, it remains unknown whether DCI-enriched Tartary buckwheat extract can ameliorate mitochondrial dysfunction, ER stress and inflammation in the endothelium...
December 7, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29219180/laminar-shear-stress-promotes-mitochondrial-homeostasis-in-endothelial-cells
#8
Li-Hong Wu, Hao-Chun Chang, Pei-Ching Ting, Danny Ling Wang
Vascular endothelial cells (ECs) are constantly subjected to flow-induced shear stress that is crucial for endothelial functions. Laminar shear stress (LSS) exerts atheroprotection to ECs. Mitochondrial homeostasis is essential for cellular survival. However, the effects of LSS on mitochondrial homeostasis in ECs remain unclear. Mitochondrial homeostasis in ECs exposed to LSS was examined. Cultured human umbilical vein ECs were subjected to LSS (12 dynes/cm2 ) generated by a parallel-plate flow chamber system...
December 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29215088/charcot-marie-tooth-disease-type-2a-with-an-autosomal-recessive-inheritance-the-first-report-of-an-adult-onset-disease
#9
Ryota Hikiami, Hirofumi Yamashita, Natsuko Koita, Naoto Jingami, Nobukatsu Sawamoto, Kaoru Furukawa, Hiromichi Kawai, Tomoya Terashima, Nobuyuki Oka, Akihiro Hashiguchi, Hiroshi Takashima, Makoto Urushitani, Ryosuke Takahashi
Axonal Charcot-Marie-Tooth disease (CMT) is most frequently caused by mutations in the MFN2 gene (CMT2A) that can lead to various clinical phenotypes. The age at disease onset varies, but most cases occur before adolescence. We report two Japanese sisters who presented with middle-age-onset peripheral neuropathy with distinct clinical features. In the affected sisters, a homozygous missense mutation, c.1894C>T, p.R632W, corresponding to the transmembrane domain of MFN2 was identified; this mutation was heterozygous in another non-affected sibling, demonstrating co-segregation of the genotype and phenotype...
November 13, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/29212658/a-new-mitofusin-topology-places-the-redox-regulated-c-terminus-in-the-mitochondrial-intermembrane-space
#10
Sevan Mattie, Jan Riemer, Jeremy G Wideman, Heidi M McBride
Mitochondrial fusion occurs in many eukaryotes, including animals, plants, and fungi. It is essential for cellular homeostasis, and yet the underlying mechanisms remain elusive. Comparative analyses and phylogenetic reconstructions revealed that fungal Fzo1 and animal Mitofusin proteins are highly diverged from one another and lack strong sequence similarity. Bioinformatic analysis showed that fungal Fzo1 proteins exhibit two predicted transmembrane domains, whereas metazoan Mitofusins contain only a single transmembrane domain...
December 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29201274/slower-dynamics-and-aged-mitochondria-in-sporadic-alzheimer-s-disease
#11
Patricia Martín-Maestro, Ricardo Gargini, Esther García, George Perry, Jesús Avila, Vega García-Escudero
Sporadic Alzheimer's disease corresponds to 95% of cases whose origin is multifactorial and elusive. Mitochondrial dysfunction is a major feature of Alzheimer's pathology, which might be one of the early events that trigger downstream principal events. Here, we show that multiple genes that control mitochondrial homeostasis, including fission and fusion, are downregulated in Alzheimer's patients. Additionally, we demonstrate that some of these dysregulations, such as diminished DLP1 levels and its mitochondrial localization, as well as reduced STOML2 and MFN2 fusion protein levels, take place in fibroblasts from sporadic Alzheimer's disease patients...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29187671/bavachin-induces-apoptosis-through-mitochondrial-regulated-er-stress-pathway-in-hepg2-cells
#12
Ying Yang, Xianglin Tang, Feiran Hao, Zengchun Ma, Yuguang Wang, Lili Wang, Yue Gao
As a traditional herbal medicine, the fruits of Psoralea corylifolia L. (FP) have been widely used for the treatment of various skin diseases for hundred years. Recently, the emerging FP-induced toxic effects, especially hepatotoxicity, in clinic are getting the public's attention. However, its exact toxic components and mechanisms underlying remain unclear. Bavachin, one of flavonoids in FP, has been documented as a hepatotoxic substance, and the present study aimed to determine the toxicity caused by bavachin and the possible toxic mechanisms involved using HepG2 cells...
November 29, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29178074/beyond-deubiquitylation-usp30-mediated-regulation-of-mitochondrial-homeostasis
#13
Jiayun Hou, Mohmmad Eldeeb, Xiangdong Wang
Mutations or sequence aberrations in the Parkin gene are among the most common causes of autosomal recessive Parkinson's disorder (PD). Parkin, a cytoplasmic E3 ubiquitin ligase, is involved in mitochondrial quality control pathways, including mitochondrial fission and mitophagy by autophagy-related genes. Parkin mediates the covalent addition of ubiquitin (Ub) chains to Lys 6, Lys 11, and Lys 63 on diverse mitochondrial-related target proteins. USP30, a mitochondrial deubiquitinase, promotes mitochondrial fusion by mediating the deubiquitination of ubiquitylated forms of mitofusins, such as Mfn1 and Mfn2...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29174527/genotypic-and-phenotypic-spectrum-of-the-most-common-causative-genes-of-charcot-marie-tooth-disease-in-hungarian-patients
#14
György Máté Milley, Edina Timea Varga, Zoltán Grosz, Csilla Nemes, Zsuzsanna Arányi, Judit Boczán, Péter Diószeghy, Mária Judit Molnár, Anikó Gál
Charcot-Marie-Tooth neuropathy (CMT) is a genetically and clinically heterogeneous group of neuromuscular disorders with an overall prevalence of 1 per 2500. Here we report the first comprehensive genetic epidemiology study of Hungarian CMT patients. 409 CMT1 and 122 CMT2 patients were enrolled and genetic testing of PMP22, GJB1, MPZ, EGR2 and MFN2 genes were performed routinely. NDRG1 and CTDP1 genes were screened only for founder mutations in Roma patients. Causative genetic mutations were identified in 67...
September 8, 2017: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/29144987/benzo-a-pyren-7-8-dihydrodiol-9-10-epoxide-induces-human-trophoblast-swan-71-cell-dysfunctions-due-to-cell-apoptosis-through-disorder-of-mitochondrial-fission-fusion
#15
Weiping Wang, Rong Wang, Qiao Zhang, Gil Mor, Huidong Zhang
Benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide (BPDE) is an endocrine disrupter and ultimate carcinogenic product of benzo(a)pyrene (BaP). Numerous studies have shown that BPDE causes trophoblast-related diseases, such as preeclampsia, growth restriction or miscarriages. However, the underlying mechanism, especially the mitochondria-related BPDE-induced trophoblast dysfunction remains unknown. In this study, we examined mitochondrial functions in BPDE-induced human trophoblast cell line Swan 71. BPDE decreased cell ability, attenuated cell invasion and HCG secretion, induced cell apoptosis, decreased mitochondrial membrane potential, increased reactive oxygen species (ROS) and MDA, and decreased SOD activity in a dose-dependent manner...
November 13, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29128369/inhibition-of-poly-adp-ribose-polymerase-1-alters-expression-of-mitochondria-related-genes-in-pc12-cells-relevance-to-mitochondrial-homeostasis-in-neurodegenerative-disorders
#16
Grzegorz A Czapski, Magdalena Cieślik, Przemysław L Wencel, Sylwia Wójtowicz, Robert P Strosznajder, Joanna B Strosznajder
Alzheimer's disease (AD) is characterized by the release of amyloid beta peptides (Aβ) in the form of monomers/oligomers which may lead to oxidative stress, mitochondria dysfunction, synaptic loss, neuroinflammation and, in consequence, to overactivation of poly(ADP-ribose) polymerase-1 (PARP-1). However, Aβ peptides are also released in the brain ischemia, traumatic injury and in inflammatory response. PARP-1 is suggested to be a promising target in therapy of neurodegenerative disorders. We investigated the impact of PARP-1 inhibition on transcription of mitochondria-related genes in PC12 cells...
November 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29123480/impairment-of-mitochondrial-biogenesis-and-dynamics-involved-in-isoniazid-induced-apoptosis-of-hepg2-cells-was-alleviated-by-p38-mapk-pathway
#17
Tianguang Zhang, Takashi Ikejima, Lizhong Li, Ruiqin Wu, Xiaoyan Yuan, Jun Zhao, Yimei Wang, Shuangqing Peng
Isoniazid (INH), a widely used first-line antitubercular drug, has been noted to be associated with hepatotoxicity. In spite of extensive researches over many decades, the mechanism of INH-induced hepatotoxicity still remains poorly understood. Recently, mitochondrial toxicity has been emerging as a new paradigm for INH-induced hepatotoxicity. In this study, we showed that INH impaired mitochondrial biogenesis and dynamics in human hepatocarcinoma HepG2 cells. INH reduced mitochondrial membrane potential (MMP) and induced mitochondria swelling...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29107503/abrogating-mitochondrial-dynamics-in-mouse-hearts-accelerates-mitochondrial-senescence
#18
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/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
#19
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/29074197/mitochondrial-dysfunction-perturbations-of-mitochondrial-dynamics-and-biogenesis-involved-in-endothelial-injury-induced-by-silica-nanoparticles
#20
Caixia Guo, Ji Wang, Li Jing, Ru Ma, Xiaoying Liu, Lifang Gao, Lige Cao, Junchao Duan, Xianqing Zhou, Yanbo Li, Zhiwei Sun
As silica nanoparticles (SiNPs) pervade the global economy, however, the followed emissions during the manufacturing, use, and disposal stages inevitably bring an environmental release, potentially result in harmful impacts. Endothelial dysfunction precedes cardiovascular disease, and is often accompanied by mitochondrial impairment and dysfunction. We had reported endothelial dysfunction induced by SiNPs, however, the related mechanisms by which SiNPs interact with mitochondria are not well understood. In the present study, we examined SiNPs-induced mitochondrial dysfunction, and further demonstrated their adverse effects on mitochondrial dynamics and biogenesis in endothelial cells (HUVECs)...
October 24, 2017: Environmental Pollution
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