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https://www.readbyqxmd.com/read/29774638/loss-of-sirtuin-1-and-mitofusin-2-contributes-to-enhanced-ischemia-reperfusion-injury-in-aged-livers
#1
Sung Kook Chun, Sooyeon Lee, Joseph Flores-Toro, Rebecca Y U, Ming-Jim Yang, Kristina L Go, Thomas G Biel, Catherine E Miney, Schiley Pierre Louis, Brian K Law, Mary E Law, Elizabeth M Thomas, Kevin E Behrns, Christiaan Leeuwenburgh, Jae-Sung Kim
Ischemia/reperfusion (I/R) injury is a causative factor contributing to morbidity and mortality during liver resection and transplantation. Livers from elderly patients have a poorer recovery from these surgeries, indicating reduced reparative capacity with aging. Mechanisms underlying this age-mediated hypersensitivity to I/R injury remain poorly understood. Here, we investigated how sirtuin 1 (SIRT1) and mitofusin 2 (MFN2) are affected by I/R in aged livers. Young (3 months) and old (23-26 months) male C57/BL6 mice were subjected to hepatic I/R in vivo...
May 17, 2018: Aging Cell
https://www.readbyqxmd.com/read/29762821/the-influencing-mechanism-of-mtor-signal-pathway-mediated-by-mitofusin-2-in-development-of-follicle
#2
Q-Y Luo, P Huo, L-L Wang, X-H Wu
OBJECTIVE: To investigate the influencing mechanism of mammalian target of rapamycin (mTOR) signal pathway mediated by mitofusin-2 (Mfn2) in the development of follicle. MATERIALS AND METHODS: We selected 20 healthy Sprague Dawley (SD) female rats aging between 6 and 8 weeks were divided into the control group and the polycystic ovarian syndrome (PCOS) model group. Rats in PCOS group received the lavage using 0.4 mL 1% carboxymethyl cellulose solution containing letrozole (1 mg/kg/d) consecutively for 20 to 25d...
April 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29749475/mir-125a-induces-apoptosis-metabolism-disorder-and-migrationimpairment-in-pancreatic-cancer-cells-by-targeting-mfn2-related-mitochondrial-fission
#3
Lichao Pan, Lin Zhou, Weijia Yin, Jia Bai, Rong Liu
Mitochondrial fission is important for the development and progression of pancreatic cancer (PC). However, little is known regarding its role in pancreatic cancer apoptosis, metabolism and migration. In the current study, the mechanism by which mitochondrial fission modifies the biological characteristics of PC was explored. MicroRNA‑125a (miR‑125a) had the ability to inhibit mitochondrial fission and contributed to cellular survival. Suppressed mitochondrial fission led to a reduction in mitochondrial debris, preserved the mitochondrial membrane potential, inhibited mitochondrial permeability transition pore opening, ablated cytochrome c leakage into the cytoplasm and reduced the pro‑apoptotic protein contents, finally blocking mitochondria related apoptosis pathways...
April 26, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29748634/gene-by-environment-interactions-that-disrupt-mitochondrial-homeostasis-cause-neurodegeneration-in-c-elegans-parkinson-s-models
#4
Hanna Kim, Rylee J Perentis, Guy A Caldwell, Kim A Caldwell
Parkinson's disease (PD) is a complex multifactorial disorder where environmental factors interact with genetic susceptibility. Accumulating evidence suggests that mitochondria have a central role in the progression of neurodegeneration in sporadic and/or genetic forms of PD. We previously reported that exposure to a secondary metabolite from the soil bacterium, Streptomyces venezuelae, results in age- and dose-dependent dopaminergic (DA) neurodegeneration in Caenorhabditis elegans and human SH-SY5Y neurons...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29742430/manipulation-of-mitochondria-dynamics-reveals-separate-roles-for-form-and-function-in-mitochondria-distribution
#5
Tatiana Trevisan, Diana Pendin, Aldo Montagna, Sergio Bova, Anna Maria Ghelli, Andrea Daga
Mitochondria shape is controlled by membrane fusion and fission mediated by mitofusins, Opa1, and Drp1, whereas mitochondrial motility relies on microtubule motors. These processes govern mitochondria subcellular distribution, whose defects are emphasized in neurons because of their polarized structure. We have studied how perturbation of the fusion/fission balance affects mitochondria distribution in Drosophila axons. Knockdown of Marf or Opa1 resulted in progressive loss of distal mitochondria and in a distinct oxidative phosphorylation and membrane potential deficit...
May 8, 2018: Cell Reports
https://www.readbyqxmd.com/read/29734176/mitofusin-2-exerts-a-protective-role-in-ischemia-reperfusion-injury-through-increasing-autophagy
#6
Cheng Peng, Wei Rao, Lei Zhang, Fan Gao, Hao Hui, Kai Wang, Shuhui Dai, Yuefan Yang, Peng Luo, Yihui Ma, Wenke Ma, Xinguang Yu, Zhou Fei
BACKGROUND/AIMS: Autophagy is essential for maintaining cellular homeostasis and the survival of terminally differentiated cells as neurons. In this study, we aim to investigate whether mitofusin 2, a mitochondrial fusion protein, mediates autophagy in cerebral ischemia/reperfusion (I/R) injury. METHODS: Primary cultured neurons were treated with oxygen-glucose deprivation/reperfusion to mimic cerebral I/R injury in vitro. Autophagosomes were visualized upon TEM...
May 3, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29731912/the-anti-tumor-effects-of-mfn2-in-breast-cancer-are-dependent-on-promoter-dna-methylation-the-p21-ras-motif-and-pka-phosphorylation-site
#7
Yufeng Li, Wenyue Dong, Xijin Shan, Hui Hong, Yan Liu, Yankun Liu, Xiaohui Liu, Xiaojun Zhang, Jinghua Zhang
Mitofusin 2 ( Mfn2 ) is expressed in numerous human tissues and serves a pivotal role in cell proliferation. However, Mfn2 is considered as an anti-tumor gene, and is silenced in human malignant tumors, including those of breast cancer. However, the mechanisms contributing to Mfn2 silencing and the mechanism of its anti-tumor function in breast cancer remain unclear. In the present study, hypoexpression of Mfn2 , and hypermethylation of its promoter, was confirmed in human breast cancer cells and in breast cancer tissues by reverse transcription-quantitative polymerase chain reaction (PCR) and methylation specific PCR, respectively...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29721168/recruitment-of-mitofusin-2-into-lipid-rafts-drives-mitochondria-fusion-induced-by-mdivi-1
#8
Laura Ciarlo, Rosa Vona, Valeria Manganelli, Lucrezia Gambardella, Carla Raggi, Matteo Marconi, Walter Malorni, Maurizio Sorice, Tina Garofalo, Paola Matarrese
The regulation of the mitochondrial dynamics and the balance between fusion and fission processes are crucial for the health and fate of the cell. Mitochondrial fusion and fission machinery is controlled by key proteins such as mitofusins, OPA-1 and several further molecules. In the present work we investigated the implication of lipid rafts in mitochondrial fusion induced by Mdivi-1. Our results underscore the possible implication of lipid "rafts" in mitochondrial morphogenetic changes and their homeostasis...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29715546/tdp-43-interacts-with-mitochondrial-proteins-critical-for-mitophagy-and-mitochondrial-dynamics
#9
Stephani A Davis, Sheed Itaman, Christopher M Khalid-Janney, Justin A Sherard, James A Dowell, Nigel J Cairns, Michael A Gitcho
Transactive response DNA-binding protein of 43 kDa (TDP-43) functions as a heterogeneous nuclear ribonucleoprotein and is the major pathological protein in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). TDP-43 pathology may also be present as a comorbidity in approximately 20-50% of sporadic Alzheimer's disease cases. In a mouse model of MND, full-length TDP-43 increases association with the mitochondria and blocking the TDP-43/mitochondria interaction ameliorates motor dysfunction...
April 30, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29710722/mitochondrial-dysfunction-as-a-predictor-and-driver-of-alzheimer-s-disease-like-pathology-in-oxys-rats
#10
Mikhail A Tyumentsev, Natalia A Stefanova, Natalia A Muraleva, Yulia V Rumyantseva, Elena Kiseleva, Valentin A Vavilin, Nataliya G Kolosova
Growing evidence suggests that mitochondrial dysfunction is an early event in sporadic Alzheimer's disease (AD), but the impact of mitochondrial dysfunction on the transition from healthy aging to AD remains elusive. Here we estimated the influence of mitochondrial dysfunction on the initiation of AD signs in OXYS rats, which simulate key characteristics of sporadic AD. We assessed the mitochondrial ultrastructure of pyramidal neurons of the hippocampus at the age preceding the development (age 20 days), during manifestation (4-5 months), and at the well-pronounced stages (18-24 months) of the AD-like pathology in OXYS rats...
April 27, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29687234/ros-as-regulators-of-mitochondrial-dynamics-in-neurons
#11
REVIEW
Carolina Cid-Castro, Diego Rolando Hernández-Espinosa, Julio Morán
Mitochondrial dynamics is a complex process, which involves the fission and fusion of mitochondrial outer and inner membranes. These processes organize the mitochondrial size and morphology, as well as their localization throughout the cells. In the last two decades, it has become a spotlight due to their importance in the pathophysiological processes, particularly in neurological diseases. It is known that Drp1, mitofusin 1 and 2, and Opa1 constitute the core of proteins that coordinate this intricate and dynamic process...
April 23, 2018: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/29674596/mfn2-agonists-reverse-mitochondrial-defects-in-preclinical-models-of-charcot-marie-tooth-disease-type-2a
#12
Agostinho G Rocha, Antonietta Franco, Andrzej M Krezel, Jeanne M Rumsey, Justin M Alberti, William C Knight, Nikolaos Biris, Emmanouil Zacharioudakis, James W Janetka, Robert H Baloh, Richard N Kitsis, Daria Mochly-Rosen, R Reid Townsend, Evripidis Gavathiotis, Gerald W Dorn
Mitofusins (MFNs) promote fusion-mediated mitochondrial content exchange and subcellular trafficking. Mutations in Mfn2 cause neurodegenerative Charcot-Marie-Tooth disease type 2A (CMT2A). We showed that MFN2 activity can be determined by Met376 and His380 interactions with Asp725 and Leu727 and controlled by PINK1 kinase-mediated phosphorylation of adjacent MFN2 Ser378 Small-molecule mimics of the peptide-peptide interface of MFN2 disrupted this interaction, allosterically activating MFN2 and promoting mitochondrial fusion...
April 20, 2018: Science
https://www.readbyqxmd.com/read/29672614/adaptation-of-motor-unit-contractile-properties-in-rat-medial-gastrocnemius-to-treadmill-endurance-training-relationship-to-muscle-mitochondrial-biogenesis
#13
Katarzyna Kryściak, Joanna Majerczak, Jakub Kryściak, Dawid Łochyński, Dominik Kaczmarek, Hanna Drzymała-Celichowska, Piotr Krutki, Anna Gawedzka, Magdalena Guzik, Michał Korostynski, Zbigniew Szkutnik, Elżbieta Pyza, Wiesława Jarmuszkiewicz, Jerzy A Zoladz, Jan Celichowski
This study aimed at investigating the effects of 2, 4 and 8 weeks of endurance training on the contractile properties of slow (S), fast fatigue resistant (FR) and fast fatigable (FF) motor units (MUs) in rat medial gastrocnemius (MG) in relation to the changes in muscle mitochondrial biogenesis. The properties of functionally isolated MUs were examined in vivo. Mitochondrial biogenesis was judged based on the changes in mitochondrial DNA copy number (mtDNA), the content of the electron transport chain (ETC) proteins and PGC-1α in the MG...
2018: PloS One
https://www.readbyqxmd.com/read/29671706/circadian-regulation-of-mitochondrial-dynamics-in-retinal-photoreceptors
#14
Janet Ya-An Chang, Liheng Shi, Michael L Ko, Gladys Y-P Ko
Energy expenditure and metabolism in the vertebrate retina are under circadian control, as we previously reported that the overall retinal ATP content and various signaling molecules related to metabolism display daily or circadian rhythms. Changes in the fission and fusion process of mitochondria, the major organelles producing ATP, in retinal photoreceptors are largely dependent on light exposure, but whether mitochondrial dynamics in photoreceptors and retinal neurons are under circadian control is not clear...
April 2018: Journal of Biological Rhythms
https://www.readbyqxmd.com/read/29661855/the-heptad-repeat-domain-1-of-mitofusin-has-membrane-destabilization-function-in-mitochondrial-fusion
#15
Frédéric Daste, Cécile Sauvanet, Andrej Bavdek, James Baye, Fabienne Pierre, Rémi Le Borgne, Claudine David, Manuel Rojo, Patrick Fuchs, David Tareste
Mitochondria are double-membrane-bound organelles that constantly change shape through membrane fusion and fission. Outer mitochondrial membrane fusion is controlled by Mitofusin, whose molecular architecture consists of an N-terminal GTPase domain, a first heptad repeat domain (HR1), two transmembrane domains, and a second heptad repeat domain (HR2). The mode of action of Mitofusin and the specific roles played by each of these functional domains in mitochondrial fusion are not fully understood. Here, using a combination of in situ and in vitro fusion assays, we show that HR1 induces membrane fusion and possesses a conserved amphipathic helix that folds upon interaction with the lipid bilayer surface...
April 16, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29621777/loading-mir-210-in-endothelial-progenitor-cells-derived-exosomes-boosts-their-beneficial-effects-on-hypoxia-reoxygeneation-injured-human-endothelial-cells-via-protecting-mitochondrial-function
#16
Xiaotang Ma, Jinju Wang, Jiao Li, Chunlian Ma, Shuzhen Chen, Wei Lei, Yi Yang, Shiming Liu, Ji Bihl, Can Chen
BACKGROUND/AIMS: Stem cell-derived exosomes (EXs) offer protective effects on various cells via their carried microRNAs (miRs). Meanwhile, miR-210 has been shown to reduce mitochondrial reactive oxygen species (ROS) overproduction. In this study, we determined the potential effects of endothelial progenitor cell-derived EXs (EPC-EXs) on hypoxia/ reoxygenation (H/R) injured endothelial cells (ECs) and investigated whether these effects could be boosted by miR-210 loading. METHODS: Human EPCs were used to generate EPC-EXs, or transfected with scrambler control or miR-210 mimics to generate EPC-EXssc and EPC-EXsmiR-210...
March 29, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29602237/nefa-induced-ros-impaired-insulin-signalling-through-the-jnk-and-p38mapk-pathways-in-non-alcoholic-steatohepatitis
#17
Wenwen Gao, Xiliang Du, Lin Lei, Heyuan Wang, Min Zhang, Zhe Wang, Xiaobing Li, Guowen Liu, Xinwei Li
The aim of this study was to investigate the changes in hepatic oxidative phosphorylation (OXPHOS) complexes (COs) in patients and cows with non-alcoholic steatohepatitis (NASH) and to investigate the mechanism that links mitochondrial dysfunction and hepatic insulin resistance induced by non-esterified fatty acids (NEFAs). Patients and cows with NASH displayed high blood NEFAs, TNF-α and IL-6 concentrations, mitochondrial dysfunction and insulin resistance. The protein levels of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), mitofusin-2 (Mfn-2) and OXPHOS complexes (human: COI and COIII; cow: COI-IV) were significantly decreased in patients and cows with NASH...
March 30, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29587277/mitofusin-2-triggers-cervical-carcinoma-cell-hela-apoptosis-via-mitochondrial-pathway-in-mouse-model
#18
Weiqiong Wang, Xiaowen Liu, Xiaomei Guo, Huanhuan Quan
BACKGROUND/AIMS: Cervical carcinoma continues to be one of the most dangerous cancer types, and more effective therapies are urgently needed for cervical carcinoma treatment. Mitochondria-associated Mitofusin 2 has influence on the progression of many cancers. In the current study, we aimed to focus on the cell apoptotic effects of Mfn2 on cervical carcinoma HeLa cells in vitro and to try to explore its underlying mechanisms. Moreover, we investigated the anticancer potential of Mfn2 in a cervical carcinoma mouse model...
March 20, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29563863/mitofusin-dependent-er-stress-triggers-glial-dysfunction-and-nervous-system-degeneration-in-a-drosophila-model-of-friedreich-s-ataxia
#19
Oliver Edenharter, Stephan Schneuwly, Juan A Navarro
Friedreich's ataxia (FRDA) is the most important recessive ataxia in the Caucasian population. It is caused by a deficit of the mitochondrial protein frataxin. Despite its pivotal effect on biosynthesis of iron-sulfur clusters and mitochondrial energy production, little is known about the influence of frataxin depletion on homeostasis of the cellular mitochondrial network. We have carried out a forward genetic screen to analyze genetic interactions between genes controlling mitochondrial homeostasis and Drosophila frataxin...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29558204/microtubule-associated-tumor-suppressor-1-interacts-with-mitofusins-to-regulate-mitochondrial-morphology-in-endothelial-cells
#20
Yinfang Wang, Yitong Huang, Youbin Liu, Jinping Li, Yilong Hao, Peihao Yin, Zongjun Liu, Jingzhou Chen, Ying Wang, Nanping Wang, Peng Zhang
Mitochondria are dynamic organelles that are able to change their morphology and cellular distribution by either fission or fusion. However, the molecular mechanisms controlling mitochondrial dynamics in vascular endothelial cells (ECs) remain largely unknown. In this study, we observed that knock down of microtubule-associated tumor suppressor 1 (MTUS1) in ECs inhibited tube formation and migration, accompanied with decreased promigratory signalings. We showed that MTUS1 was localized in the outer membrane of mitochondria in ECs...
March 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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