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https://www.readbyqxmd.com/read/28539410/leishmania-donovani-restricts-mitochondrial-dynamics-to-enhance-mirnp-stability-and-target-rna-repression-in-host-macrophages
#1
Yogaditya Chakrabarty, Suvendra N Bhattacharyya
microRNAs (miRNA), the tiny regulatory RNAs, form complex with Argonaute (Ago) proteins and inhibit gene expression in metazoan cells. While studying parasite invaded macrophages, we have identified a unique mode of gene regulation, where the parasite Leishmania donovani (Ld) causes mitochondrial depolarization, reduces mitochondrial dynamics and restricts turnover of cellular microRNA ribonucleoprotein (miRNP) complexes in infected host cells. This leads to increased stability of miRNPs along with elevated level of Ago2 bound cytokine mRNA in Ld infected macrophages...
May 24, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28539390/mfn2-deletion-in-brown-adipose-tissue-protects-from-insulin-resistance-and-impairs-thermogenesis
#2
Kiana Mahdaviani, Ilan Y Benador, Shi Su, Raffi A Gharakhanian, Linsey Stiles, Kyle M Trudeau, Maria Cardamone, Violeta Enríquez-Zarralanga, Eleni Ritou, Tamar Aprahamian, Marcus F Oliveira, Barbara E Corkey, Valentina Perissi, Marc Liesa, Orian S Shirihai
BAT-controlled thermogenic activity is thought to be required for its capacity to prevent the development of insulin resistance. This hypothesis predicts that mediators of thermogenesis may help prevent diet-induced insulin resistance. We report that the mitochondrial fusion protein Mitofusin 2 (Mfn2) in BAT is essential for cold-stimulated thermogenesis, but promotes insulin resistance in obese mice. Mfn2 deletion in mice through Ucp1-cre (BAT-Mfn2-KO) causes BAT lipohypertrophy and cold intolerance. Surprisingly however, deletion of Mfn2 in mice fed a high fat diet (HFD) results in improved insulin sensitivity and resistance to obesity, while impaired cold-stimulated thermogenesis is maintained...
May 24, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28536949/exercise-and-doxorubicin-treatment-modulate-cardiac-mitochondrial-quality-control-signaling
#3
I Marques-Aleixo, E Santos-Alves, J R Torrella, P J Oliveira, J Magalhães, A Ascensão
The cross-tolerance effect of exercise against heart mitochondrial-mediated quality control, remodeling and death-related mechanisms associated with sub-chronic Doxorubicin (DOX) treatment is yet unknown. We therefore analyzed the effects of two distinct chronic exercise models (endurance treadmill training-TM and voluntary free wheel activity-FW) performed during the course of the sub-chronic DOX treatment on mitochondrial susceptibility to permeability transition pore (mPTP), apoptotic and autophagic signaling and mitochondrial dynamics...
May 23, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28527631/the-thiol-switch-c684-in-mitofusin-2-mediates-redox-induced-alterations-of-mitochondrial-shape-and-respiration
#4
Osamah Thaher, Christina Wolf, Partha Narayan Dey, Alireza Pouya, Verena Wüllner, Stefan Tenzer, Axel Methner
Mitofusin-2 (MFN2) is a GTPase in the outer mitochondrial membrane involved in the regulation of mitochondrial fusion and bioenergetics. MFN2 also plays a role in mitochondrial fusion induced by changes in the intracellular redox state. Adding oxidized glutathione (GSSG), the core cellular stress indicator, to mitochondrial preparations stimulates mitochondrial fusion by inducing disulphide bond-mediated oligomer formation of MFN2 and its homolog MFN1 which involve cysteine 684 (C684) of MFN2. Mitochondrial hyperfusion represents an adaptive stress response that confers transient protection by increasing mitochondrial ATP production but how this depends on the thiol switch C684 in MFN2 has not been investigated...
May 17, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28518143/calcium-sensing-receptor-protects-high-glucose-induced-energy-metabolism-disorder-via-blocking-gp78-ubiquitin-proteasome-pathway
#5
Yuehong Wang, Ping Gao, Can Wei, Hongzhu Li, Li Zhang, Yajun Zhao, Bo Wu, Ye Tian, Weihua Zhang, Lingyun Wu, Rui Wang, Changqing Xu
Diabetic cardiomyopathy (DCM) is a major complication and fatal cause of the patients with diabetes. The calcium sensing receptor (CaSR) is a G protein-coupled receptor, which is involved in maintaining calcium homeostasis, regulating cell proliferation and apoptosis, and so on. In our previous study, we found that CaSR expression, intracellular calcium levels and cardiac function were all significantly decreased in DCM rats; however, the exact mechanism are not clear yet. The present study revealed the protective role of CaSR in myocardial energy metabolism disorder induced by high glucose (HG) as well as the underlying mechanism...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28513770/association-between-mfn2-gene-polymorphisms-and-the-risk-and-prognosis-of-acute-liver-failure-a-case-control-study-in-a-chinese-population
#6
Y-L Wei, Q Tian, X-X Zhao, G-Z Qiu, Y Xu
This study aimed to determine the role of mitofusin 2 (MFN2) gene polymorphisms in the risk and prognosis of acute liver failure (ALF). A total of 298 blood samples were collected from 138 ALF patients (case group) and 160 healthy participants (control group). Coagulation function, glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), total bilirubin (TB), blood ammonia and lactic acid (LA) were measured. The predictive evaluation of MFN2 gene polymorphisms in the risk and prognosis of ALF patients was estimated using Kaplan-Meier survival analysis, haplotype analysis, binary logistic regression analysis and Cox regression analysis...
May 15, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28503736/hydrogen-sulfide-pretreatment-improves-mitochondrial-function-in-myocardial-hypertrophy-via-a-sirt3-dependent-manner
#7
Guoliang Meng, Jieqiong Liu, Shangmin Liu, Qiuyi Song, Lulu Liu, Liping Xie, Yi Han, Yong Ji
BACKGROUND AND PURPOSE Hydrogen sulfide (H2 S) is a gaseous signal molecule with anti-oxidative ability. Sirtuin 3 (SIRT3) is closely associated with mitochondrial function and oxidative stress. The study was to investigate whether and how H2 S improved myocardial hypertrophy via a SIRT3-dependent manner. EXPERIMENTAL APPROACH Neonatal rat cardiomyocytes were pre-treated with NaHS (50 μM) for 4 h followed by angiotensin II (Ang II, 100 nM) for 24 h. SIRT3 was silenced with siRNA technology. SIRT 3 promoter activity and expression, cell surface, hypertrophic gene mRNA expression, mitochondrial oxygen consumption rate and membrane potential were measured...
May 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28487236/upregulation-of-mir-195-accelerates-oxidative-stress-induced-retinal-endothelial-cell-injury-by-targeting-mitofusin-2-in-diabetic-rats
#8
Rui Zhang, Qian Garrett, Huimin Zhou, Xiaoxi Wu, Yueran Mao, Ximing Cui, Bing Xie, Zanchao Liu, Dongsheng Cui, Lei Jiang, Qingfu Zhang, Shunjiang Xu
This study was performed to investigate the oxidative stress-induced miRNA changes in relation to pathogenesis of diabetic retinopathy (DR) and to establish a functional link between miRNAs and oxidative stress-induced retinal endothelial cell injury. Our results demonstrated that oxidative stress could induce alterations of miRNA expression profile, including up-regulation of miR-195 in the diabetic retina or cultured HMRECs after exposed to H2O2 or HG (P < 0.05). Oxidative stress also resulted in a significant reduction of MFN2 expression in diabetic retina or HMRECs (P < 0...
May 6, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28483668/doxorubicin-induced-cardiomyocyte-apoptosis-role-of-mitofusin-2
#9
Han Tang, Aibin Tao, Jia Song, Qian Liu, Hao Wang, Tao Rui
BACKGROUND: Doxorubicin (DOX) is an anti-tumor agent that is widely used in clinical setting for cancer treatment. The application of the DOX, however, is limited by its cardiac toxicity which can induce heart failure through an undefined mechanism. Mitofusin 2 (Mfn2) is a mitochondrial GTPase fusion protein that is located on the outer membrane of mitochondria (OMM). The Mfn2 plays an important role in mitochondrial fusion and fission. The aim of this study is to identify the role of the Mfn2 in DOX-induced cardiomyocyte apoptosis...
May 5, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28473727/cryptolepine-inhibits-melanoma-cell-growth-through-coordinated-changes-in-mitochondrial-biogenesis-dynamics-and-metabolic-tumor-suppressor-ampk%C3%AE-1-2-lkb1
#10
Harish C Pal, Ram Prasad, Santosh K Katiyar
Dysregulated mitochondrial dynamics and biogenesis have been associated with various pathological conditions including cancers. Here, we assessed the therapeutic effect of cryptolepine, a pharmacologically active alkaloid derived from the roots of Cryptolepis sanguinolenta, on melanoma cell growth. Treatment of human melanoma cell lines (A375, Hs294t, SK-Mel28 and SK-Mel119) with cryptolepine (1.0, 2.5, 5.0 and 7.5 μM) for 24 and 48 h significantly (P < 0.001) inhibited the growth of melanoma cells but not normal melanocytes...
May 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28463235/perturbations-in-the-apoptotic-pathway-and-mitochondrial-network-dynamics-in-peripheral-blood-mononuclear-cells-from-bipolar-disorder-patients
#11
G Scaini, G R Fries, S S Valvassori, C P Zeni, G Zunta-Soares, M Berk, J C Soares, J Quevedo
Bipolar disorder (BD) is a severe psychiatric disorder characterized by phasic changes of mood and can be associated with progressive structural brain change and cognitive decline. The numbers and sizes of glia and neurons are reduced in several brain areas, suggesting the involvement of apoptosis in the pathophysiology of BD. Because the changes in mitochondrial dynamics are closely related with the early process of apoptosis and the specific processes of apoptosis and mitochondrial dynamics in BD have not been fully elucidated, we measured the apoptotic pathway and the expression of mitochondrial fission/fusion proteins from BD patients and healthy controls...
May 2, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28455958/csfv-induced-mitochondrial-fission-and-mitophagy-to-inhibit-apoptosis
#12
Hongchao Gou, Mingqiu Zhao, Hailuan Xu, Jin Yuan, Wencheng He, Mengjiao Zhu, Hongxing Ding, Lin Yi, Jinding Chen
Classical swine fever virus (CSFV), which causes typical clinical characteristics in piglets, including hemorrhagic syndrome and immunosuppression, is linked to hepatitis C and dengue virus. Oxidative stress and a reduced mitochondrial transmembrane potential are disturbed in CSFV-infected cells. The balance of mitochondrial dynamics is essential for cellular homeostasis. In this study, we offer the first evidence that CSFV induces mitochondrial fission and mitophagy to inhibit host cell apoptosis for persistent infection...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28438761/improved-skeletal-muscle-ca-2-regulation-in-vivo-following-contractions-in-mice-overexpressing-pgc-1%C3%AE
#13
Hiroaki Eshima, Shinji Miura, Nanami Senoo, Koji Hatakeyama, David C Poole, Yutaka Kano
In skeletal muscle, resting intracellular Ca(2+) concentration ([Ca(2+)]i) homeostasis is exquisitely regulated by Ca(2+) transport across the sarcolemmal, mitochondrial and sarcoplasmic reticulum (SR) membranes. Of these three systems, the relative importance of the mitochondria in [Ca(2+)]i regulation remains poorly understood in in vivo skeletal muscle. We tested the hypothesis that the capacity for Ca(2+) uptake by mitochondria is a primary factor in determining [Ca(2+)]i regulation in muscle at rest and following contractions...
April 24, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28414270/human-biallelic-mfn2-mutations-induce-mitochondrial-dysfunction-upper-body-adipose-hyperplasia-and-suppression-of-leptin-expression
#14
Nuno Rocha, David A Bulger, Andrea Frontini, Hannah Titheradge, Sigrid Bjerge Gribsholt, Rachel Knox, Matthew Page, Julie Harris, Felicity Payne, Claire Adams, Alison Sleigh, John Crawford, Anette Prior Gjesing, Jette Bork-Jensen, Oluf Pedersen, Inês Barroso, Torben Hansen, Helen Cox, Mary Reilly, Alex Rossor, Rebecca J Brown, Simeon I Taylor, Duncan McHale, Martin Armstrong, Elif A Oral, Vladimir Saudek, Stephen O'Rahilly, Eamonn R Maher, Bjørn Richelsen, David B Savage, Robert K Semple
MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane fusion and inter-organelle communication. MFN2 mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently associated with upper body adipose overgrowth. We describe similar massive adipose overgrowth with suppressed leptin expression in four further patients with biallelic MFN2 mutations and at least one p.Arg707Trp allele. Overgrown tissue was composed of normal-sized, UCP1-negative unilocular adipocytes, with mitochondrial network fragmentation, disorganised cristae, and increased autophagosomes...
April 19, 2017: ELife
https://www.readbyqxmd.com/read/28410195/antagonistic-effects-of-selenium-on-lead-induced-autophagy-by-influencing-mitochondrial-dynamics-in-the-spleen-of-chickens
#15
Yujing Han, Chunqiu Li, Mingjun Su, Zhihui Wang, Ning Jiang, Dongbo Sun
Lead (Pb) may damage the immune function in human and animal. Selenium (Se) has antagonistic effects on Pb. In our study, brown layer chickens were randomly allocated to control group, Se group (1 mg/kg Se), Se+Pb group (1 mg/kg Se and 350 mg/kg Pb), and Pb group (350 mg/kg Pb). The chickens were sacrificed on the 90th day; spleen tissues were subjected to observation of ultrastructure and detection of spleen-related indexes. The results revealed that in the Pb group, expression levels of the cytokines IL-1 and TNF-α significantly increased, and expression levels of IL-2 and INF-γ significantly decreased; activities of antioxidant enzyme GPX, SOD and CAT significantly decreased, and expression level of malondialdehyde (MDA) significantly increased; expression levels of mitochondrial fission-related genes (Mff and Drp1) significantly increased, and expression levels of mitochondrial fusion-related genes (Opa1, Mfn1 and Mfn2) significantly decreased; expression of autophagy-related genes (Beclin 1, Dynein, Atg 5, LC3-I and LC-II) was upregulated, while expression of mammalian target of rapamycin (mTOR) was downregulated...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406974/resveratrol-reduces-the-apoptosis-induced-by-cigarette-smoke-extract-by-upregulating-mfn2
#16
Chao Song, Bailing Luo, Li Gong
PURPOSE: The aim of this study was to investigate the effect of resveratrol (RSV) on cigarette smoke extract (CSE)-induced cell apoptosis and mitochondrial dysfunction in vitro, as well as changes in the MFN2 expression level. METHODS: Cultured human bronchial epithelial (HBE) cells were initially treated with CSE to induce apoptosis, followed by incubation either with or without RSV. Numerous techniques were used to evaluate the outcomes of the present study, including a cell counting kit-8 assay, real-time quantitative polymerase chain reaction (real-time qPCR), western blotting, JC-1 fluorescence, Hoechst 33342 staining, Annexin V-PI flow cytometry apoptosis analyses, and siRNA technology...
2017: PloS One
https://www.readbyqxmd.com/read/28381463/chronic-kidney-disease-induces-autophagy-leading-to-dysfunction-of-mitochondria-in-skeletal-muscle
#17
Zhen Su, Janet D Klein, Jie DU, Harold A Franch, Liping Zhang, Faten Hassounah, Matthew B Hudson, Xiaonan H Wang
Chronic kidney disease (CKD) causes loss of lean body mass by multiple mechanisms. This study examines whether autophagy-mediated proteolysis contributes to CKD-induced muscle wasting. We tested autophagy in the muscle of CKD mice with plantaris muscle overloading to mimic resistance exercise or with acupuncture plus low frequency electrical stimulation (Acu/LFES) treatment. In CKD muscle, Bnip3, Beclin-1, LC3II mRNAs and proteins were increased compared with control muscle, indicating autophagosome-lysosome formation induction...
April 5, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28380071/the-abundance-of-the-arl2-gtpase-and-its-gap-elmod2-at-mitochondria-are-modulated-by-the-fusogenic-activity-of-mitofusins-and-stressors
#18
Laura E Newman, Cara R Schiavon, Chengjing Zhou, Richard A Kahn
Mitochondria are essential, dynamic organelles that respond to a number of stressors with changes in morphology that are linked to several mitochondrial functions, though the mechanisms involved are poorly understood. We show that the levels of the regulatory GTPase ARL2 and its GAP, ELMOD2, are specifically increased at mitochondria in immortalized mouse embryo fibroblasts deleted for Mitofusin 2 (MFN2), but not MFN1. Elevated ARL2 and ELMOD2 in MEFs deleted for MFN2 could be reversed by re-introduction of MFN2, but only when the mitochondrial fragmentation in these MEFs was also reversed, demonstrating that reversal of elevated ARL2 and ELMOD2 requires the fusogenic activity of MFN2...
2017: PloS One
https://www.readbyqxmd.com/read/28356907/neuroprotective-effect-and-mechanism-of-thiazolidinedione-on-dopaminergic-neurons-in-vivo-and-in-vitro-in-parkinson-s-disease
#19
Yanqin Wang, Weilin Zhao, Ge Li, Jinhu Chen, Xin Guan, Xi Chen, Zhenlong Guan
The aim of the present study was to gain insight into the neuroprotection effects and mechanism of thiazolidinedione pioglitazone in both in vitro and in vivo MPP(+)/MPTP induced PD models. In vivo experimental results showed that oral treatment of pioglitazone resulted in significant improvements in behavior symptoms damaged by MPTP and increase in the survival of TH positive neurons in the pioglitazone intervention groups. In addition, oral treatment of pioglitazone increased the expression of peroxisome proliferator-activated receptor-γ coactivator of 1α (PGC-1α) and increased the number of mitochondria, along with an observed improvement in mitochondrial ultrastructure...
2017: PPAR Research
https://www.readbyqxmd.com/read/28348166/mfn2-is-critical-for-brown-adipose-tissue-thermogenic-function
#20
Marie Boutant, Sameer S Kulkarni, Magali Joffraud, Joanna Ratajczak, Miriam Valera-Alberni, Roy Combe, Antonio Zorzano, Carles Cantó
Mitochondrial fusion and fission events, collectively known as mitochondrial dynamics, act as quality control mechanisms to ensure mitochondrial function and fine-tune cellular bioenergetics. Defective mitofusin 2 (Mfn2) expression and enhanced mitochondrial fission in skeletal muscle are hallmarks of insulin-resistant states. Interestingly, Mfn2 is highly expressed in brown adipose tissue (BAT), yet its role remains unexplored. Using adipose-specific Mfn2 knockout (Mfn2-adKO) mice, we demonstrate that Mfn2, but not Mfn1, deficiency in BAT leads to a profound BAT dysfunction, associated with impaired respiratory capacity and a blunted response to adrenergic stimuli...
March 27, 2017: EMBO Journal
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