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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/29744667/vagus-nerve-stimulation-exerts-cardioprotection-against-myocardial-ischemia-reperfusion-injury-predominantly-through-its-efferent-vagal-fibers
#4
Watthana Nuntaphum, Wanpitak Pongkan, Suwakon Wongjaikam, Savitree Thummasorn, Pongpan Tanajak, Juthamas Khamseekaew, Kannaporn Intachai, Siriporn C Chattipakorn, Nipon Chattipakorn, Krekwit Shinlapawittayatorn
Vagus nerve stimulation (VNS) has been shown to exert cardioprotection against myocardial ischemia/reperfusion (I/R) injury. However, whether the cardioprotection of VNS is mainly due to direct activation through its ipsilateral efferent fibers (motor) rather than indirect effects mediated by the afferent fibers (sensory) have not been clearly understood. We hypothesized that VNS exerts cardioprotection predominantly through its efferent vagal fibers. Thirty swine (30-35 kg) were randomized into five groups: I/R no VNS (I/R), and left mid-cervical VNS with both vagal trunks intact (LC-VNS), with left vagus nerve transection (LtVNX), with right vagus nerve transection (RtVNX) and with atropine pretreatment (Atropine), respectively...
May 9, 2018: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29734176/mitofusin-2-exerts-a-protective-role-in-ischemia-reperfusion-injury-through-increasing-autophagy
#5
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
#6
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/29727016/metabolic-stress-dependent-regulation-of-the-mitochondrial-biogenic-molecular-response-to-high-intensity-exercise-in-human-skeletal-muscle
#7
M Fiorenza, T P Gunnarsson, M Hostrup, F M Iaia, F Schena, H Pilegaard, J Bangsbo
KEY POINTS: Low-volume high-intensity exercise training promotes muscle mitochondrial adaptations that resemble the ones associated with high-volume moderate-intensity exercise training. These training-induced mitochondrial adaptations stem from the cumulative effects of transient transcriptional responses to each acute exercise bout. However, whether metabolic stress is a key mediator of the acute molecular responses to high-intensity exercise is still incompletely understood. Herein we show that, by comparing different work-matched low-volume high-intensity exercise protocols, more marked metabolic perturbations were associated with enhanced mitochondrial biogenesis-related muscle mRNA responses...
May 4, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29715546/tdp-43-interacts-with-mitochondrial-proteins-critical-for-mitophagy-and-mitochondrial-dynamics
#8
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
#9
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/29701781/mutant-app-and-amyloid-beta-induced-defective-autophagy-mitophagy-mitochondrial-structural-and-functional-changes-and-synaptic-damage-in-hippocampal-neurons-from-alzheimer-s-disease
#10
P Hemachandra Reddy, XiangLin Yin, Maria Manczak, Subodh Kumar, Pradeepkiran Jangampalli Adi, Murali Vijayan, Arubala P Reddy
The purpose of our study was to determine the toxic effects of hippocampal mutant APP and amyloid beta (Aβ) in human mutant APP (mAPP) cDNA transfected with primary mouse hippocampal neurons (HT22). Hippocampal tissues are the best source of studying learning and memory functions in patients with Alzheimer's disease (AD) and healthy controls. However, investigating immortalized hippocampal neurons that express AD proteins provide an excellent opportunity for drug testing. Using quantitative RT-PCR, immunoblotting & immunofluorescence, and transmission electron microscopy, we assessed mRNA and protein levels of synaptic, autophagy, mitophagy, mitochondrial dynamics, biogenesis, dendritic protein MAP2, and assessed mitochondrial number and length in mAPP-HT22 cells that express Swedish/Indiana mutations...
April 25, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29682760/protective-role-of-parkin-in-skeletal-muscle-contractile-and-mitochondrial-function
#11
Gilles Gouspillou, Richard Godin, Jérome Piquereau, Martin Picard, Mahroo Mofarrahi, Jasmin Mathew, Fennigje M Purves-Smith, Nicolas Sgarioto, Russell T Hepple, Yan Burelle, Sabah Na Hussain
KEY POINTS SUMMARY: Parkin, an E3 ubiquitin ligase encoded by the Park2 gene, has been implicated in the regulation of mitophagy, a quality control process whereby defective mitochondria are degraded. The exact physiological significance of Parkin in regulating mitochondrial function and contractility in skeletal muscle remains largely unexplored. Using Park2-/- mice, we show that Parkin ablation causes a decrease in muscle specific force, a severe decrease in mitochondrial respiration, mitochondrial uncoupling and an increased susceptibility to opening of the permeability transition pore...
April 22, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29676259/mfn2-ubiquitination-by-pink1-parkin-gates-the-p97-dependent-release-of-er-from-mitochondria-to-drive-mitophagy
#12
Gian-Luca McLelland, Thomas Goiran, Wei Yi, Geneviève Dorval, Carol X Chen, Nadine D Lauinger, Andrea I Krahn, Sepideh Valimehr, Aleksandar Rakovic, Isabelle Rouiller, Thomas M Durcan, Jean-François Trempe, Edward A Fon
Despite their importance as signaling hubs, the function of mitochondria-ER contact sites in mitochondrial quality control pathways remains unexplored. Here we describe a mechanism by which Mfn2, a mitochondria-ER tether, gates the autophagic turnover of mitochondria by PINK1 and parkin. Mitochondria-ER appositions are destroyed during mitophagy, and reducing mitochondria-ER contacts increases the rate of mitochondrial degradation. Mechanistically, parkin/PINK1 catalyze a rapid burst of Mfn2 phosphoubiquitination to trigger p97-dependent disassembly of Mfn2 complexes from the outer mitochondrial membrane, dissociating mitochondria from the ER...
April 20, 2018: ELife
https://www.readbyqxmd.com/read/29674596/mfn2-agonists-reverse-mitochondrial-defects-in-preclinical-models-of-charcot-marie-tooth-disease-type-2a
#13
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
#14
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
#15
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/29658057/combined-effects-of-rat-schwann-cells-and-17%C3%AE-estradiol-in-a-spinal-cord-injury-model
#16
Zeinab Namjoo, Fateme Moradi, Roya Aryanpour, Abbas Piryaei, Mohammad Taghi Joghataei, Yusef Abbasi, Amir Hosseini, Sajad Hassanzadeh, Fatemeh Ranjbar Taklimie, Cordian Beyer, Adib Zendedel
Spinal cord injury (SCI) is a devastating traumatic event which burdens the affected individuals and the health system. Schwann cell (SC) transplantation is a promising repair strategy after SCI. However, a large number of SCs do not survive following transplantation. Previous studies demonstrated that 17β-estradiol (E2) protects different cell types and reduces tissue damage in SCI experimental animal model. In the current study, we evaluated the protective potential of E2 on SCs in vitro and investigated whether the combination of hormonal and SC therapeutic strategy has a better effect on the outcome after SCI...
April 15, 2018: Metabolic Brain Disease
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
#17
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/29608912/glomerular-mitochondrial-changes-in-hiv-associated-renal-injury
#18
Joseph L Bryant, Poornachander R Guda, Girma Asemu, Rogin Subedi, Sugata Ray, Omar S Khalid, Vivek Shukla, Dhruvil Patel, Harry Davis, Vamshi K C Nimmagadda, Tapas K Makar
HIV-associated nephropathy (HIVAN) is an AIDs-related disease of the kidney. HIVAN is characterized by severe proteinuria, podocyte hyperplasia, collapse, glomerular, and tubulointerstitial damage. HIV-1 transgenic (Tg26) mouse is the most popular model to study the HIV manifestations that develop similar renal presentations as HIVAN. Viral proteins, including Tat, Nef, and Vpr play a significant role in renal cell damage. It has been shown that mitochondrial changes are involved in several kidney diseases, and therefore, mitochondrial dysfunction may be implicated in the pathology of HIVAN...
March 30, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29587277/mitofusin-2-triggers-cervical-carcinoma-cell-hela-apoptosis-via-mitochondrial-pathway-in-mouse-model
#19
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/29545887/role-of-mitofusin-2-in-the-protective-effect-of-breviscapine-against-hepatic-ischemia-reperfusion-injury-in-rats
#20
Zhen Bao, Weijun Chen, Fan Pan, Bo Peng, Jin Gong
The purpose of the present study was to investigate the effect of breviscapine injection on hepatic ischemia/reperfusion (I/R) injury in rats. To explore the relevance and discuss the underlying mechanism of mitofusin 2 (Mfn2) in hepatic I/R injury, 40 Sprague-Dawley male rats were randomly and equally divided into five groups (n=8 per group) as follows: Sham, I/R + normal saline 1 (NS1), I/R + breviscapine 1 (Bre1), I/R + NS2 and I/R + Bre2 groups. Groups 1 and 2 represented ischemia for 20 and 60 min, respectively...
April 2018: Experimental and Therapeutic Medicine
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