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https://www.readbyqxmd.com/read/28919853/p47phox-cdk5-drp1-mediated-mitochondrial-fission-evokes-pv-cell-degeneration-in-the-rat-dentate-gyrus-following-status-epilepticus
#1
Ji-Eun Kim, Tae-Cheon Kang
Parvalbumin (PV) is one of the calcium-binding proteins, which plays an important role in the responsiveness of inhibitory neurons to an adaptation to repetitive spikes. Furthermore, PV neurons are highly vulnerable to status epilepticus (SE, prolonged seizure activity), although the underlining mechanism remains to be clarified. In the present study, we found that p47Phox expression was transiently and selectively increased in PV neurons 6 h after SE. This up-regulated p47Phox expression was accompanied by excessive mitochondrial fission...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28918902/mtor-controls-mitochondrial-dynamics-and-cell-survival-via-mtfp1
#2
Masahiro Morita, Julien Prudent, Kaustuv Basu, Vanessa Goyon, Sakie Katsumura, Laura Hulea, Dana Pearl, Nadeem Siddiqui, Stefan Strack, Shawn McGuirk, Julie St-Pierre, Ola Larsson, Ivan Topisirovic, Hojatollah Vali, Heidi M McBride, John J Bergeron, Nahum Sonenberg
The mechanisms that link environmental and intracellular stimuli to mitochondrial functions, including fission/fusion, ATP production, metabolite biogenesis, and apoptosis, are not well understood. Here, we demonstrate that the nutrient-sensing mechanistic/mammalian target of rapamycin complex 1 (mTORC1) stimulates translation of mitochondrial fission process 1 (MTFP1) to control mitochondrial fission and apoptosis. Expression of MTFP1 is coupled to pro-fission phosphorylation and mitochondrial recruitment of the fission GTPase dynamin-related protein 1 (DRP1)...
September 13, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28915614/mitochondrial-protein-18-mtp18-plays-a-pro-apoptotic-role-in-chemotherapy-induced-gastric-cancer-cell-apoptosis
#3
Lynn H H Aung, Ruibei Li, Bellur S Prabhakar, Ajay V Maker, Peifeng Li
One of the severe limitations of chemotherapy is the development of drug resistance. However, the mechanisms underlying chemotherapy resistance remain to be elucidated. Mitochondrial mediated apoptosis is a form of cell death induced by chemotherapy. Several chemotherapeutic agents have been shown to induce mitochondrial fission, and finally activate the apoptosis cascade in various cancer cells. Here, we report that the mitochondrial membrane protein 18 (MTP18) induced mitochondrial fragmentation in gastric cancer cells under doxorubicin (DOX) exposure...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28911913/phosphatidic-acid-and-cardiolipin-coordinate-mitochondrial-dynamics
#4
REVIEW
Shoichiro Kameoka, Yoshihiro Adachi, Koji Okamoto, Miho Iijima, Hiromi Sesaki
Membrane organelles comprise both proteins and lipids. Remodeling of these membrane structures is controlled by interactions between specific proteins and lipids. Mitochondrial structure and function depend on regulated fusion and the division of both the outer and inner membranes. Here we discuss recent advances in the regulation of mitochondrial dynamics by two critical phospholipids, phosphatidic acid (PA) and cardiolipin (CL). These two lipids interact with the core components of mitochondrial fusion and division (Opa1, mitofusin, and Drp1) to activate and inhibit these dynamin-related GTPases...
September 11, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28893839/mitochondrial-fission-facilitates-the-selective-mitophagy-of-protein-aggregates
#5
Jonathon L Burman, Sarah Pickles, Chunxin Wang, Shiori Sekine, Jose Norberto S Vargas, Zhe Zhang, Alice M Youle, Catherine L Nezich, Xufeng Wu, John A Hammer, Richard J Youle
Within the mitochondrial matrix, protein aggregation activates the mitochondrial unfolded protein response and PINK1-Parkin-mediated mitophagy to mitigate proteotoxicity. We explore how autophagy eliminates protein aggregates from within mitochondria and the role of mitochondrial fission in mitophagy. We show that PINK1 recruits Parkin onto mitochondrial subdomains after actinonin-induced mitochondrial proteotoxicity and that PINK1 recruits Parkin proximal to focal misfolded aggregates of the mitochondrial-localized mutant ornithine transcarbamylase (ΔOTC)...
September 11, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28891994/mdivi-1-protects-adult-rat-hippocampal-neural-stem-cells-against-palmitate-induced-oxidative-stress-and-apoptosis
#6
Sehee Kim, Chanyang Kim, Seungjoon Park
Palmitate concentrations in type 2 diabetic patients are higher than in healthy subjects. The prolonged elevation of plasma palmitate levels induces oxidative stress and mitochondrial dysfunction in neuronal cells. In this study, we examined the role of mdivi-1, a selective inhibitor of mitochondrial fission protein dynamin-regulated protein 1 (Drp1), on the survival of cultured hippocampal neural stem cells (NSCs) exposed to high palmitate. Treatment of hippocampal NSCs with mdivi-1 attenuated palmitate-induced increase in cell death and apoptosis...
September 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28890359/optic-atrophy-1-mediates-coenzyme-q-responsive-regulation-of-respiratory-complex-iv-activity-in-brain-mitochondria
#7
Kazuhide Takahashi, Ikuroh Ohsawa, Takuji Shirasawa, Mayumi Takahashi
The oxygen consumption rate (OCR) in brain mitochondria is significantly lower in aged mice than in young mice, and the reduced OCR is rescued by administration of water-solubilized CoQ10 to aged mice via drinking water. However, the mechanism behind this remains unclear. Here, we show that the activity of respiratory complex IV (CIV) in brain mitochondria declined in aged mice than in young mice, with no significant change in individual respiratory complex levels and their supercomplex assembly. Reduced CIV activity in the aged mice coincided with reduced binding of optic atrophy 1 (OPA1) to CIV...
September 7, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28889229/melatonin-alleviates-inflammation-induced-apoptosis-in-human-umbilical-vein-endothelial-cells-via-suppression-of-ca-2-xo-ros-drp1-mitochondrial-fission-axis-by-activation-of-ampk-serca2a-pathway
#8
Jiasen Cui, Zeng Li, Shunjiu Zhuang, Shaohong Qi, Li Li, Junwen Zhou, Wan Zhang, Yun Zhao
Endothelia inflammation damage is vital to the development and progression of chronic venous disease. In the present study, we explored the protective effect of melatonin on endothelia apoptosis induced by LPS, particularly focusing on the mitochondrial fission. We demonstrated that human umbilical vein endothelial cells (HUVEC) subjected to LPS for 12 h exhibited a higher apoptotic rate. However, melatonin (1-20 μM) treatment 12 h before LPS had the ability to protect HUVEC cell against LPS-mediated apoptosis in a dose-dependent manner...
September 9, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28888871/interplay-of-mitochondria-apoptosis-regulatory-factors-and-micrornas-in-valvular-heart-disease
#9
Muhammad Ishtiaq Jan, Riaz Anwar Khan, Tahir Ali, Muhammad Bilal, Long Bo, Abdul Sajid, Abdul Malik, Naseeb Urehman, Nayyar Waseem, Javed Nawab, Murad Ali, Abdul Majeed, Hamid Ahmad, Sohail Aslam, Sadia Hamera, Aneesa Sultan, Mariam Anees, Qamar Javed, Iram Murtaza
Valvular heart disease (VHD) is an active process involving a wide range of pathological changes. The major complications of VHD are stenosis and regurgitation, which are macroscopic phenomena, induced in part through cellular changes. Altered expression of mitochondria associated genes causes membrane potential depolarization, leading to the increased levels of apoptosis observed in cardiac dysfunction. Objective of this study is to find molecular medicine candidates that can control expression of the key mitochondria apoptosis regulatory genes...
September 6, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28878368/cryo-em-studies-of-drp1-reveal-cardiolipin-interactions-that-activate-the-helical-oligomer
#10
Christopher A Francy, Ryan W Clinton, Chris Fröhlich, Colleen Murphy, Jason A Mears
Dynamins are mechano-chemical GTPases involved in the remodeling of cellular membranes. In this study, we have investigated the mechanism of dynamin-related protein 1 (Drp1), a key mediator of mitochondrial fission. To date, it is unclear how Drp1 assembles on the mitochondrial outer membrane in response to different lipid signals to induce membrane fission. Here, we present cryo-EM structures of Drp1 helices on nanotubes with distinct lipid compositions to mimic membrane interactions with the fission machinery...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28878259/promoting-drp1-mediated-mitochondrial-fission-in-midlife-prolongs-healthy-lifespan-of-drosophila-melanogaster
#11
Anil Rana, Matheus P Oliveira, Andy V Khamoui, Ricardo Aparicio, Michael Rera, Harry B Rossiter, David W Walker
The accumulation of dysfunctional mitochondria has been implicated in aging, but a deeper understanding of mitochondrial dynamics and mitophagy during aging is missing. Here, we show that upregulating Drp1-a Dynamin-related protein that promotes mitochondrial fission-in midlife, prolongs Drosophila lifespan and healthspan. We find that short-term induction of Drp1, in midlife, is sufficient to improve organismal health and prolong lifespan, and observe a midlife shift toward a more elongated mitochondrial morphology, which is linked to the accumulation of dysfunctional mitochondria in aged flight muscle...
September 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28860994/pioglitazone-improves-mitochondrial-function-in-the-remnant-kidney-and-protects-against-renal-fibrosis-in-5-6-nephrectomized-rats
#12
Li Sun, Quan Yuan, Tianhua Xu, Li Yao, Jiangmin Feng, Jianfei Ma, Lining Wang, Changlong Lu, Danan Wang
Pioglitazone is a type of peroxisome proliferator-activated receptor γ (PPARγ) agonist and has been demonstrated to be effective in chronic kidney diseases (CKD) treatment. However, the underlying mechanism involved in the renoprotection of pioglitazone has not been fully revealed. In the present study, the renoprotective mechanism of pioglitazone was investigated in 5/6 nephrectomized (Nx) rats and TGF-β1-exposed HK-2 cells. Pioglitazone attenuated renal injury and improved renal function, as examined by 24 h urinary protein, blood urea nitrogen and plasma creatinine in Nx rats...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28859978/carbonyl-cyanide-3-chlorophenylhydrazone-cccp-suppresses-sting-mediated-dna-sensing-pathway-through-inducing-mitochondrial-fission
#13
Dohyeong Kwon, Eunbyeol Park, Hiromi Sesaki, Suk-Jo Kang
Besides its important role in innate immune response to DNA virus infection, the regulatory function of STING in autoimmunity and cancer is emerging. Recently, multiple mechanisms regulating the activity of the STING pathway have been revealed. Previous study showed that carbonyl cyanide 3-chlorophenylhydrazone (CCCP), the protonophore, inhibited STING-mediated IFN-β production via disrupting mitochondrial membrane potential (MMP). However, how MMP dissipation leads to the suppression of the STING pathway remains unknown...
August 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28859443/imbalance-in-mitochondrial-dynamics-and-apoptosis-in-pregnancies-among-hiv-infected-women-on-haart-with-obstetric-complications
#14
Mariona Guitart-Mampel, A Sandra Hernandez, Constanza Moren, Marc Catalan-Garcia, Ester Tobias, Ingrid Gonzalez-Casacuberta, Diana L Juarez-Flores, Josep M Gatell, Francesc Cardellach, Jose C Milisenda, Josep M Grau, Eduard Gratacos, Francesc Figueras, Gloria Garrabou
Background: HIV infection and HAART trigger genetic and functional mitochondrial alterations leading to cell death and adverse clinical manifestations. Mitochondrial dynamics enable mitochondrial turnover and degradation of damaged mitochondria, which may lead to apoptosis. Objectives: To evaluate markers of mitochondrial dynamics and apoptosis in pregnancies among HIV-infected women on HAART and determine their potential association with obstetric complications...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28854701/aqua-soluble-ddq-reduces-the-levels-of-drp1-and-a%C3%AE-and-inhibits-abnormal-interactions-between-a%C3%AE-and-drp1-and-protects-alzheimer-s-disease-neurons-from-a%C3%AE-and-drp1-induced-mitochondrial-and-synaptic-toxicities
#15
Chandra Sekhar Kuruva, Maria Manczak, Xiangling Yin, Gilbert Ogunmokun, Arubala P Reddy, P Hemachandra Reddy
The purpose of our study was to develop a therapeutic target that can reduce Aβ and Drp1 levels, and also can inhibit abnormal interactions between Aβ and Drp1 in AD neurons. To achieve this objective, we designed various compounds and their 3-dimensional molecular structures were introduced into Aβ and Drp1 complex and identified their inhibitory properties against Aβ-Drp1 interaction. Among all, DDQ was selected for further investigation because of 1) its best docking score and 2) its binding capability at interacting sites of Drp1 and Aβ complex...
September 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28842943/to-mdivi-1-or-not-to-mdivi-1-is-that-the-question
#16
REVIEW
George Smith, Gianluca Gallo
The fission/division and fusion of mitochondria are fundamental aspects of mitochondrial biology. The balance of fission and fusion sets the length of mitochondria in cells to serve their physiological requirements. The fission of mitochondria is markedly induced in many disease states and in response to cellular injury, resulting in the fragmentation of mitochondria into dysfunctional units. The mechanism that drives fission is dependent on the dynamin related protein 1 (Drp1) GTPase. mdivi-1 is a quinazolinone originally described as a selective inhibitor of Drp1, over other dynamin family members, and reported to inhibit mitochondrial fission...
August 26, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28842472/the-constriction-and-scission-machineries-involved-in-mitochondrial-fission
#17
REVIEW
Felix Kraus, Michael T Ryan
A key event in the evolution of eukaryotic cells was the engulfment of an aerobic bacterium by a larger anaerobic archaebacterium, leading to a close relationship between the host and the newly formed endosymbiont. Mitochondria, originating from this event, have evolved to be the main place of cellular ATP production. Maintaining elements of their independence, mitochondria undergo growth and division in the cell, thereby ensuring that new daughter cells inherit a mitochondrial complement. Mitochondrial division is also important for other processes, including quality control, mitochondrial (mt)DNA inheritance, transport and cell death...
August 25, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28841174/purification-preliminary-characterization-and-hepatoprotective-effects-of-polysaccharides-from-dandelion-root
#18
Liangliang Cai, Dongwei Wan, Fanglian Yi, Libiao Luan
In this study, purification, preliminary characterization and hepatoprotective effects of water-soluble polysaccharides from dandelion root (DRP) were investigated. Two polysaccharides, DRP1 and DRP2, were isolated from DRP. The two polysaccharides were α-type polysaccharides and didn't contain protein. DRP1, with a molecular weight of 5695 Da, was composed of glucose, galactose and arabinose, whereas DRP2, with molecular weight of 8882 Da, was composed of rhamnose, galacturonic acid, glucose, galactose and arabinose...
August 25, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28841143/extract-of-sheng-mai-san-ameliorates-myocardial-ischemia-induced-heart-failure-by-modulating-ca-2-calcineurin-mediated-drp1-signaling-pathways
#19
Ye Yang, Yushan Tian, Siyao Hu, Suxia Bi, Suxia Li, Yuanjia Hu, Junping Kou, Jin Qi, Boyang Yu
Sheng-Mai-San (SMS) is a well-known traditional Chinese medicine (TCM) complex prescription used to treat heart failure (HF) and angina in clinic. However, its potential therapeutic mechanisms remain unclear. The present study evaluated the cardioprotection of extract of SMS (ESMS) on myocardial ischemia (MI)-induced HF, and explored the underlying molecular mechanisms. The results demonstrated that ESMS (728.0 mg/kg) significantly attenuated MI injury-induced HF by improving cardiac function and pathological changes, decreasing lactate dehydrogenase (LDH), creatine kinase (CK) activities, and brain natriuretic peptide (BNP) levels; increasing ATPase activity; and reducing intracellular Ca(2+) levels in MI-induced HF mice model...
August 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28838842/ellagic-acid-antagonizes-bnip3-mediated-mitochondrial-injury-and-necrotic-cell-death-of-cardiac-myocytes
#20
Abhinav Dhingra, Rahul Jayas, Pegah Afshar, Matthew Guberman, Graham Maddaford, Johnathan Gerstein, Brooke Lieberman, Hilary Nepon, Victoria Margulets, Rimpy Dhingra, Lorrie A Kirshenbaum
The Bcl-2 protein Bnip3 is crucial for provoking oxidative injury to mitochondria following anthracycline treatment or ischemia-reperfusion injury. Herein, we investigate the effects of the polyphenolic compound ellagic acid (EA) on Bnip3 mediated mitochondrial injury and necrotic cell death in cardiac myocytes. In contrast to vehicle treated cardiomyocytes, Bnip3 was highly enriched in mitochondrial fractions of cardiac myocytes treated with the anthracycline doxorubicin or in cells subjected to hypoxia (HPX)...
August 25, 2017: Free Radical Biology & Medicine
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