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https://www.readbyqxmd.com/read/28108329/exercise-increases-mitochondrial-complex-i-activity-and-drp1-expression-in-the-brains-of-aged-mice
#1
Aaron M Gusdon, Jason Callio, Giovanna DiStefano, Robert M O'Doherty, Bret H Goodpaster, Paul M Coen, Charleen T Chu
Exercise is known to have numerous beneficial effects. Recent studies indicate that exercise improves mitochondrial energetics not only in skeletal muscle but also in other tissues. While exercise elicits positive effects on memory, neurogenesis, and synaptic plasticity, the effects of exercise on brain mitochondrial energetics remain relatively unknown. Herein, we studied the effects of exercise training in old and young mice on brain mitochondrial energetics, in comparison to known effects on peripheral tissues that utilize fatty acid oxidation...
January 17, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28106052/tanshinone-iia-induces-intrinsic-apoptosis-in-osteosarcoma-cells-both-in-vivo-and-in-vitro-associated-with-mitochondrial-dysfunction
#2
Sheng-Teng Huang, Chao-Chun Huang, Wen-Liang Huang, Tsu-Kung Lin, Pei-Lin Liao, Pei-Wen Wang, Chia-Wei Liou, Jiin-Haur Chuang
Tanshinone IIA (Tan IIA), a phytochemical derived from the roots of Salvia miltiorrhiza, has been shown to inhibit growth and induce apoptosis in various cancer cells. The association of its inhibitory effect on the primary malignant bone tumor, osteosarcoma, with mitochondrial dysfunction remains unclear. This study aimed to investigate the anti-proliferative effects of Tan IIA on human osteosarcoma 143B cells both in vitro and in vivo. Administration of Tan IIA to NOD-SCID mice implanted with 143B cells led to significant inhibition of tumor development...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28100784/mitochondrial-o-glcnac-transferase-mogt-regulates-mitochondrial-structure-function-and-survival-in-hela-cells
#3
Juliana L Sacoman, Raul Y Dagda, Amanda R Burnham-Marusich, Ruben K Dagda, Patricia M Berninsone
O-linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAcylation of target proteins and regulates numerous biological processes. OGT is encoded by a single gene that yields nucleocytosolic and mitochondrial isoforms. To date, the role of the mitochondrial isoform of OGT (mOGT) remains largely unknown. Using high-throughput proteomics, we identified 84 candidate mitochondrial glycoproteins, of which 44 are novel. Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH: ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28098754/drp1-dependent-mitochondrial-fission-plays-critical-roles-in-physiological-and-pathological-progresses-in-mammals
#4
REVIEW
Chenxia Hu, Yong Huang, Lanjuan Li
Current research has demonstrated that mitochondrial morphology, distribution, and function are maintained by the balanced regulation of mitochondrial fission and fusion, and perturbation of the homeostasis between these processes has been related to cell or organ dysfunction and abnormal mitochondrial redistribution. Abnormal mitochondrial fusion induces the fragmentation of mitochondria from a tubular morphology into pieces; in contrast, perturbed mitochondrial fission results in the fusion of adjacent mitochondria...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28088331/eicosapentaenoic-acid-ameliorates-palmitate-induced-lipotoxicity-via-the-amp-kinase-dynamin-related-protein-1-signaling-pathway-in-differentiated-h9c2-myocytes
#5
Atsushi Sakamoto, Masao Saotome, Prottoy Hasan, Terumori Satoh, Hayato Ohtani, Tsuyoshi Urushida, Hideki Katoh, Hiroshi Satoh, Hideharu Hayashi
BACKGROUND: Emerging evidence suggested the preferable effects of eicosapentaenoic acid (EPA; n-3 polyunsaturated fatty acid) against cardiac lipotoxicity, which worsens cardiac function by means of excessive serum free fatty acids due to chronic adrenergic stimulation under heart failure. Nonetheless, the precise molecular mechanisms remain elusive. In this study, we focused on dynamin-related protein-1 (Drp1) as a possible modulator of the EPA-mediated cardiac protection against cardiac lipotoxicity, and investigated the causal relation between AMP-activated protein kinase (AMPK) and Drp1...
January 11, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28087886/d-chiro-inositol-ameliorates-endothelial-dysfunction-via-inhibition-of-oxidative-stress-and-mitochondrial-fission
#6
Bobo Zhang, Xudan Guo, Yunlong Li, Qiang Peng, Jinfeng Gao, Baolin Liu, Min Wang
SCOPE: D-chiro inositol (DCI), an isomer of inositol, possesses anti-oxidative and endothelial protective properties. The mechanism by which DCI prevents endothelial dysfunction was investigated, with emphasis on oxidative stress. METHODS AND RESULTS: DCI was found to inhibit NOX4 induction and enhance Nrf2 activity in palmitate (PA)-stimulated cells, showing that DCI prevents oxidative stress. DCI suppressed Ser616 phosphorylation and increased Ser637 phosphorylation of Drp1 and inhibited PA-induced mitochondrial fission...
January 14, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28075229/altered-mitochondrial-dynamics-as-a-consequence-of-venezuelan-equine-encephalitis-virus-infection
#7
Forrest Keck, Taryn Brooks-Faulconer, Tyler Lark, Pavitra Ravishankar, Charles Bailey, Carolina Salvador-Morales, Aarthi Narayanan
Mitochondria are sentinel organelles that are impacted by various forms of cellular stress, including viral infections. While signaling events associated with mitochondria, including those activated by pathogen associated molecular patterns (PAMPs), are widely studied, alterations in mitochondrial distribution and changes in mitochondrial dynamics are also beginning to be associated with cellular insult. Cells of neuronal origin have been demonstrated to display remarkable alterations in several instances, including neurodegenerative disorders...
January 11, 2017: Virulence
https://www.readbyqxmd.com/read/28071871/harmonization-of-mangiferin-on-methylmercury-engendered-mitochondrial-dysfunction
#8
Shubhankar Das, Ajanta Paul, Kamalesh D Mumbrekar, Satish B S Rao
Mangiferin (MGN), a C-glucosylxanthone abundantly found in mango plants, was studied for its potential to ameliorate methylmercury (MeHg) induced mitochondrial damage in HepG2 (human hepatocarcinoma) cell line. Cell viability experiments performed using 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide (MTT) showed protective property of MGN in annulling MeHg-induced cytotoxicity. Conditioning the cells with optimal dose of MGN (50 µM) lowered MeHg-induced oxidative stress, calcium influx/efflux, depletion of mitochondrial trans-membrane potential and prevented mitochondrial fission as observed by decrease in Mitotracker red fluorescence, expression of pDRP1 (serine 616), and DRP1 levels...
February 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28063983/loss-of-laforin-or-malin-results-in-increased-drp1-level-and-concomitant-mitochondrial-fragmentation-in-lafora-disease-mouse-models
#9
Mamta Upadhyay, Saloni Agarwal, Pratibha Bhadauriya, Subramaniam Ganesh
Lafora disease (LD) is an autosomal recessive form of a fatal disorder characterized by the myoclonus epilepsy, ataxia, psychosis, dementia, and dysarthria. A hallmark of LD is the presence of abnormal glycogen inclusions called Lafora bodies in the affected tissues including the neurons. LD can be caused by defects either in the laforin phosphatase coded by the EPM2A gene or in the malin E3 ubiquitin ligase coded by the NHLRC1 gene. The mouse models of LD, created by the targeted disruption of the LD genes, display several neurodegenerative changes...
January 4, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28060722/polyphyllin-i-induces-mitophagic-and-apoptotic-cell-death-in-human-breast-cancer-cells-by-increasing-mitochondrial-pink1-levels
#10
Guo-Bing Li, Ruo-Qiu Fu, Han-Ming Shen, Jing Zhou, Xiao-Ye Hu, Yan-Xia Liu, Yu-Nong Li, Hong-Wei Zhang, Xin Liu, Yan-Hao Zhang, Cheng Huang, Rong Zhang, Ning Gao
The molecular mechanisms underlying the anti-breast cancer effects of polyphyllin I, a natural compound extracted from Paris polyphylla rhizomes, are not fully understood. In the present study, we found that polyphyllin I induces mitochondrial translocation of DRP1 by dephosphorylating DRP1 at Ser637, leading to mitochondrial fission, cytochrome c release from mitochondria into the cytosol and, ultimately apoptosis. Polyphyllin I also increased the stabilization of full-length PINK1 at the mitochondrial surface, leading to the recruitment of PARK2, P62, ubiquitin, and LC3B-II to mitochondria and culminating in mitophagy...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28027494/ultrastructural-evidence-for-impaired-mitochondrial-fission-in-the-aged-rhesus-monkey-dorsolateral-prefrontal-cortex
#11
Yury M Morozov, Dibyadeep Datta, Constantinos D Paspalas, Amy F T Arnsten
Dorsolateral prefrontal cortex mediates high-order cognitive functions that are impaired early in the aging process in monkeys and humans. Here, we report pronounced changes in mitochondrial morphology in dendrites of dorsolateral prefrontal cortex neurons from aged rhesus macaques. Electron microscopy paired with 3D reconstruction from serial sections revealed an age-related increase in mitochondria with thin segments that intermingled with enlarged ones, the 'mitochondria-on-a-string' phenotype, similar to those recently reported in patients with Alzheimer's disease...
December 10, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28007911/mitochondrial-morphology-and-cellular-distribution-are-altered-in-spg31-patients-and-are-linked-to-drp1-hyperphosphorylation
#12
Julie Lavie, Román Serrat, Nadège Bellance, Gilles Courtand, Jean-William Dupuy, Christelle Tesson, Isabelle Coupry, Alexis Brice, Didier Lacombe, Alexandra Durr, Giovanni Stevanin, Fréderic Darios, Rodrigue Rossignol, Cyril Goizet, Giovanni Bénard
Hereditary spastic paraplegia, SPG31, is a rare neurological disorder caused by mutations in REEP1 gene encoding the microtubule-interacting protein, REEP1. The mechanism by which REEP1-dependent processes are linked with the disease is unclear. REEP1 regulates the morphology and trafficking of various organelles via interaction with the microtubules. In this study, we collected primary fibroblasts from SPG31 patients to investigate their mitochondrial morphology. We observed that the mitochondrial morphology in patient cells was highly tubular compared with control cells...
December 22, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27993675/the-cyclophilin-d-drp1-axis-regulates-mitochondrial-fission-contributing-to-oxidative-stress-induced-mitochondrial-dysfunctions-in-sh-sy5y-cells
#13
Anqi Xiao, Xueqi Gan, Ruiqi Chen, Yanming Ren, Haiyang Yu, Chao You
Oxidative stress plays a central role in the pathogenesis of various neurodegenerative diseases. Increasing evidences have demonstrated that structural abnormalities in mitochondria are involved in oxidative stress related nerve cell damage. And Drp1 plays a critical role in mitochondrial dynamic imbalance insulted by oxidative stress-derived mitochondria. However, the status of mitochondrial fusion and fission pathway and its relationship with mitochondrial properties such as mitochondrial membrane permeability transition pore (mPTP) have not been fully elucidated...
December 18, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27993601/mitochondrial-activity-and-dynamics-changes-regarding-metabolism-in-ageing-and-obesity
#14
REVIEW
Guillermo López-Lluch
Mitochondria play an essential role in ageing and longevity. During ageing, a general deregulation of metabolism occurs, affecting molecular, cellular and physiological activities in the organism. Dysfunction of mitochondria has been associated with ageing and age-related diseases indicating their importance in the maintenance of cell homeostasis. Three major nutritional sensors, mTOR, AMPK and Sirtuins are involved in the control of mitochondrial physiology. These nutritional sensors control mitochondrial biogenesis, dynamics by regulating fusion and fission processes, and turnover through mito- and autophagy...
December 16, 2016: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/27984195/abnormal-mitochondrial-dynamics-and-impaired-mitochondrial-biogenesis-in-trigeminal-ganglion-neurons-in-a-rat-model-of-migraine
#15
Xin Dong, Xinying Guan, Keyan Chen, Shanquan Jin, Chengyun Wang, Lanyun Yan, Zhaochun Shi, Xue Zhang, Ling Chen, Qi Wan
Accumulating evidence has demonstrated a possible role of mitochondrial dysfunction in migraine pathophysiology. Migraine sufferers exhibit impaired metabolic capacity, with an increased formation of reactive oxygen species (ROS). Mitochondrial dynamics and mitochondrial biogenesis are key processes regulating mitochondrial homeostasis. The aim of this study was to explore the alterations of mitochondrial regulatory networks in a rat model of migraine induced by repeated dural stimulation with inflammatory soup (IS)...
October 28, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27973457/pedf-inhibits-the-activation-of-nlrp3-inflammasome-in-hypoxia-cardiomyocytes-through-pedf-receptor-phospholipase-a2
#16
Zhongxin Zhou, Zhu Wang, Qiuhua Guan, Fan Qiu, Yufeng Li, Zhiwei Liu, Hao Zhang, Hongyan Dong, Zhongming Zhang
The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome has been linked to sterile inflammation, which is involved in ischemic injury in myocardial cells. Pigment epithelium-derived factor (PEDF) is a multifunctional secreted glycoprotein with many biological activities, such as anti-inflammatory, antioxidant and anti-angiogenic properties. However, it is not known whether and how PEDF acts to regulate the activation of the NLRP3 inflammasome in cardiomyocytes. In the present study, we used the neonatal cardiomyocytes models of ischemia-like conditions to evaluate the mitochondrial fission and the activation of the NLRP3 inflammasome...
December 12, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27941873/sirt4-inhibits-malignancy-progression-of-nsclcs-through-mitochondrial-dynamics-mediated-by-the-erk-drp1-pathway
#17
L Fu, Q Dong, J He, X Wang, J Xing, E Wang, X Qiu, Q Li
SIRT4 is well-known for its deacetylase activity in energy metabolism, but little is known about its roles in carcinogenesis. We demonstrated that SIRT4 was decreased in 70 out of 133 non-small cell lung cancer (NSCLC) cases by immunohistochemical staining and localized in the mitochondria using confocal microscopy. Low levels of SIRT4 expression was correlated with tumor node metastasis (TNM) stage, histological type of tumor (adenocarcinoma), lymph nodal status, Ki-67 (proliferation index) and poor overall survival...
December 12, 2016: Oncogene
https://www.readbyqxmd.com/read/27932496/sonic-hedgehog-pathway-activation-increases-mitochondrial-abundance-and-activity-in-hippocampal-neurons
#18
Pamela J Yao, Uri Manor, Ronald S Petralia, Rebecca D Brose, Ryan T Y Wu, Carolyn Ott, Ya-Xian Wang, Ari Charnoff, Jennifer Lippincott-Schwartz, Mark P Mattson
Mitochondria are essential organelles whose biogenesis, structure, and function are regulated by many signaling pathways. In this study we present evidence that, in hippocampal neurons, activation of the Sonic hedgehog (Shh) signaling pathway impacts multiple aspects of mitochondria. Mitochondrial mass was increased significantly in neurons treated with Shh. Using biochemical and fluorescence imaging analyses, we show that Shh signaling activity reduces mitochondrial fission and promotes mitochondrial elongation, at least in part, via suppression of the mitochondrial fission protein dynamin-like GTPase Drp1...
December 8, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27932492/novel-regulatory-roles-of-mff-and-drp1-in-e3-ubiquitin-ligase-march5-dependent-degradation-of-mid49-and-mcl1-and-control-of-mitochondrial-dynamics
#19
Edward Cherok, Shan Xu, Sunan Li, Shweta Das, W Alex Meltzer, Michal Zalzman, Chunxin Wang, Mariusz Karbowski
MARCH5, an OMM-associated E3 ubiquitin ligase, controls mitochondrial function. Despite its importance, the mechanism and factors controlling MARCH5 activity are largely unknown. Here we report that the MARCH5 C-terminal domain plays a critical role in degradation of MARCH5 substrates, likely by facilitating release of ubiquitinated proteins from the OMM. We also found that the mitochondrial fission proteins Drp1 and Mff negatively regulate MARCH5's activity toward MiD49 and Mcl1. Knockouts of either Drp1 or Mff led to reduced expression, shorter half-lives, and increased ubiquitination of MiD49 and Mcl1...
December 8, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27932069/quercetin-attenuates-vascular-calcification-by-inhibiting-oxidative-stress-and-mitochondrial-fission
#20
Lei Cui, Zhong Li, Xueying Chang, Guangting Cong, Lirong Hao
Vascular calcification is a strong independent predictor of increased cardiovascular morbidity and mortality and has a high prevalence among patients with chronic kidney disease. The present study investigated the effects of quercetin on vascular calcification caused by oxidative stress and abnormal mitochondrial dynamics both in vitro and in vivo. Calcifying vascular smooth muscle cells (VSMCs) treated with inorganic phosphate (Pi) exhibited mitochondrial dysfunction, as demonstrated by decreased mitochondrial potential and ATP production...
December 5, 2016: Vascular Pharmacology
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