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Mitochondria fission

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https://www.readbyqxmd.com/read/28432138/inhibition-of-drp1-ameliorates-synaptic-depression-a%C3%AE-deposition-and-cognitive-impairment-in-alzheimer-s-disease-model
#1
Seung-Hyun Baek, So Jung Park, Jae In Jeong, Sung Hyun Kim, Jihoon Han, Jae Won Kyung, Sang-Ha Baik, Yuri Choi, Bo-Youn Choi, Jinsu Park, Gahee Bahn, Ji Hyun Shin, Doo Sin Jo, Joo-Yong Lee, Choon-Gon Jang, Thiruma V Arumugam, Jongpil Kim, Jeung-Whan Han, Jae-Young Koh, Dong-Hyung Cho, Dong-Gyu Jo
Excessive mitochondrial fission is a prominent early event, and contributes to mitochondrial dysfunction, synaptic failure and neuronal cell death in the progression of Alzheimer's disease (AD). However, it remains to be determined whether inhibition of excessive mitochondrial fission is beneficial in mammal models of AD. To determine whether dynamin-related protein 1 (Drp1), a key regulator of mitochondrial fragmentation, can be a disease-modifying therapeutic target for AD, we examine the effects of Drp1 inhibitor on mitochondrial and synaptic dysfunctions induced by oligomeric β-amyloid (Aβ) in neurons, and neuropathology and cognitive functions in APP/PS1 double transgenic AD mice...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28427098/opa1-in-lipid-metabolism-function-of-opa1-in-lipolysis-and-thermogenesis-of-adipocytes
#2
Dinh-Toi Chu, Yang Tao, Kjetil Taskén
OPA1 (Optic Atrophy 1) is a mitochondrial GTPase known to regulate fission of mitochondria. It was recently also shown to locate on lipid droplets in adipocytes where it functions as an A-kinase anchoring protein (AKAP) that mediates adrenergic control of lipolysis by facilitating PKA phosphorylation of perilipin (Plin1). In brown adipocytes indirect evidence support the notion that OPA1 regulation of fission serves to increase thermogenesis, which thereby contributes to dissipation of energy. In white adipocytes, OPA1 located on lipid droplets serves as a gatekeeper to control lipolysis induced by adrenergic agonists...
April 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28423497/drp1-dependent-mitophagy-protects-against-cisplatin-induced-apoptosis-of-renal-tubular-epithelial-cells-by-improving-mitochondrial-function
#3
Chuanyan Zhao, Zhuyun Chen, Jia Qi, Suyan Duan, Zhimin Huang, Chengning Zhang, Lin Wu, Ming Zeng, Bo Zhang, Ningning Wang, Huijuan Mao, Aihua Zhang, Changying Xing, Yanggang Yuan
Cisplatin chemotherapy often causes acute kidney injury (AKI) in cancer patients. There is increasing evidence that mitochondrial dysfunction plays an important role in cisplatin-induced nephrotoxicity. Degradation of damaged mitochondria is carried out by mitophagy. Although mitophagy is considered of particular importance in protecting against AKI, little is known of the precise role of mitophagy and its molecular mechanisms during cisplatin-induced nephrotoxicity. Also, evidence that activation of mitophagy improved mitochondrial function is lacking...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418387/mitochondria-are-the-powerhouses-of-immunity
#4
REVIEW
Evanna L Mills, Beth Kelly, Luke A J O'Neill
Recent evidence indicates that mitochondria lie at the heart of immunity. Mitochondrial DNA acts as a danger-associated molecular pattern (DAMP), and the mitochondrial outer membrane is a platform for signaling molecules such as MAVS in RIG-I signaling, and for the NLRP3 inflammasome. Mitochondrial biogenesis, fusion and fission have roles in aspects of immune-cell activation. Most important, Krebs cycle intermediates such as succinate, fumarate and citrate engage in processes related to immunity and inflammation, in both innate and adaptive immune cells...
April 18, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28409745/mitochondria-division-inhibitor-1-protects-against-amyloid-%C3%AE-induced-mitochondrial-fragmentation-and-synaptic-damage-in-alzheimer-s-disease
#5
P Hemachandra Reddy, Maria Manczak, XiangLing Yin
The purpose our study was to determine the protective effects of mitochondria division inhibitor 1 (Mdivi1) in Alzheimer's disease (AD). Mdivi1 is hypothesized to reduce excessive fragmentation of mitochondria and mitochondrial dysfunction in AD neurons. Very little is known about whether Mdivi1 can confer protective effects in AD. In the present study, we sought to determine the protective effects of Mdivi1 against amyloid-β (Aβ)- and mitochondrial fission protein, dynamin-related protein 1 (Drp1)-induced excessive fragmentation of mitochondria in AD progression...
April 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28409390/dynamin-related-protein-1-as-potential-therapeutic-target-in-various-diseases
#6
REVIEW
Surinder Singh, Saurabh Sharma
Mitochondria can interchange morphology due to their dynamic nature. It can exist in either fragmented disconnected arrangement or elongated interconnected mitochondrial networks due to fission and fusion, respectively. The recent studies have revealed the remarkable and unexpected insights into the physiological impact and molecular regulation of mitochondrial morphology. The balance between fission and fusion governs the faith of the cell. The active targeting of DRP 1 to the outer mitochondrial membrane (OMM) is done by non-GTPase receptor proteins such as mitochondrial fission factor, mitochondrial fission protein 1 and mitochondrial elongation factor 1...
April 13, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28408736/mief1-2-function-as-adaptors-to-recruit-drp1-to-mitochondria-and-regulate-the-association-of-drp1-with-mff
#7
Rong Yu, Tong Liu, Shao-Bo Jin, Chenfei Ning, Urban Lendahl, Monica Nistér, Jian Zhao
Mitochondrial dynamics is a fundamental cellular process and recruitment of Drp1 to mitochondria is an essential step in mitochondrial fission. Mff and MIEF1/2 (MiD51/49) serve as key receptors for recruitment of Drp1 to mitochondria in mammals. However, if and how these receptors work together in mitochondrial fission is poorly understood. Here we show that MIEFs interact with both Drp1 and Mff on the mitochondrial surface and serve as adaptors linking Drp1 and Mff together in a trimeric Drp1-MIEF-Mff complex...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28401475/mitochondrial-quality-control-and-disease-insights-into-ischemia-reperfusion-injury
#8
REVIEW
Anthony R Anzell, Rita Maizy, Karin Przyklenk, Thomas H Sanderson
Mitochondria are key regulators of cell fate during disease. They control cell survival via the production of ATP that fuels cellular processes and, conversely, cell death via the induction of apoptosis through release of pro-apoptotic factors such as cytochrome C. Therefore, it is essential to have stringent quality control mechanisms to ensure a healthy mitochondrial network. Quality control mechanisms are largely regulated by mitochondrial dynamics and mitophagy. The processes of mitochondrial fission (division) and fusion allow for damaged mitochondria to be segregated and facilitate the equilibration of mitochondrial components such as DNA, proteins, and metabolites...
April 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28401437/estrogens-regulate-life-and-death-in-mitochondria
#9
Carolyn M Klinge
Estrogens coordinate and integrate cellular metabolism and mitochondrial activities by direct and indirect mechanisms mediated by differential expression and localization of estrogen receptors (ER) in a cell-specific manner. Estrogens regulate transcription and cell signaling pathways that converge to stimulate mitochondrial function- including mitochondrial bioenergetics, mitochondrial fusion and fission, calcium homeostasis, and antioxidant defense against free radicals. Estrogens regulate nuclear gene transcription by binding and activating the classical genomic estrogen receptors α and β (ERα and ERβ) and by activating plasma membrane-associated mERα, mERβ, and G-protein coupled ER (GPER, GPER1)...
April 11, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28391089/the-mitochondria-endoplasmic-reticulum-contact-sites-a-signalling-platform-for-cell-death
#10
REVIEW
Julien Prudent, Heidi M McBride
Mitochondria evolved as an endosymbiont providing the cell with a dizzying array of catabolic and anabolic processes essential for life. However, mitochondria have retained the ability to kill from within, and are widely considered the final executioners of programmed cell death. The groundbreaking discovery over 25 years ago that mitochondrial cytochrome c is released into the cytosol shone new and unexpected light onto this old organelle, revitalizing the field. The Bcl-2 family of proteins plays a central role in the maintenance of mitochondrial membrane integrity, but other factors are also involved in the cell death program...
April 5, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28388678/drp1-dependent-mitochondrial-fission-mediates-osteogenic-dysfunction-in-inflammation-through-elevated-production-of-reactive-oxygen-species
#11
Ling Zhang, Xueqi Gan, Yuting He, Zhuoli Zhu, Junfei Zhu, Haiyang Yu
Although previous studies have implicated pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), to be detrimental for osteogenic activity, the related regulatory mechanisms are not yet fully validated. Since mitochondria host several essential metabolic processes and play a pivotal role in cellular functions, whether and how mitochondrial function contributes to inflammation-induced bone destruction needs further exploration. Our findings revealed that TNF-α impaired osteoblast function, including decreased mRNA levels of osteogenic markers, suppressed ALP expression and activity, and compromised cellular viability...
2017: PloS One
https://www.readbyqxmd.com/read/28388446/phosphorylation-of-dynamin-related-protein-1-at-ser616-regulates-mitochondrial-fission-and-is-involved-in-mitochondrial-calcium-uniporter-mediated-neutrophil-polarization-and-chemotaxis
#12
Xianchong Zheng, Mimi Chen, Xiaojing Meng, Xinwei Chu, Chunqing Cai, Fei Zou
During an inflammatory response, polarization of neutrophils is necessary for effective chemotaxis and bacterial endocytosis. Ca(2+) uptake into mitochondria through the mitochondrial calcium uniporter (MCU) is crucial for cell metabolism, signaling and survival; however, the physiological role of MCU in human neutrophils remains unclear. Here we show that MCU is vital for the polarization and chemotaxis of neutrophils. Activation of MCU by spermine promotes neutrophil polarization and chemotaxis, whereas inhibition of MCU by Ru360 blunts both processes...
April 4, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28386844/toll-like-receptor-4-mediates-vascular-remodeling-in-hyperhomocysteinemia
#13
REVIEW
Anastasia Familtseva, Nevena Jeremic, George H Kunkel, Suresh C Tyagi
Although hyperhomocysteinemia (HHcy) is known to promote downstream pro-inflammatory cytokine elevation, the precise mechanism is still unknown. One of the possible receptors that could have significant attention in the field of hypertension is toll-like receptor 4 (TLR-4). TLR-4 is a cellular membrane protein that is ubiquitously expressed in all cell types of the vasculature. Its mutation can attenuate the effects of HHcy-mediated vascular inflammation and mitochondria- dependent cell death that suppresses hypertension...
April 6, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28384228/doxycycline-protects-against-ros-induced-mitochondrial-fragmentation-and-iso-induced-heart-failure
#14
Adam Riba, Laszlo Deres, Krisztian Eros, Aliz Szabo, Klara Magyar, Balazs Sumegi, Kalman Toth, Robert Halmosi, Eszter Szabados
In addition to their anti-bacterial action, tetracyclines also have complex biological effects, including the modification of mitochondrial protein synthesis, metabolism and gene-expression. Long-term clinical studies have been performed using tetracyclines, without significant side effects. Previous studies demonstrated that doxycycline (DOX), a major tetracyclin antibiotic, exerted a protective effect in animal models of heart failure; however, its exact molecular mechanism is still unknown. Here, we provide the first evidence that DOX reduces oxidative stress-induced mitochondrial fragmentation and depolarization in H9c2 cardiomyocytes and beneficially alters the expression of Mfn-2, OPA-1 and Drp-1 -the main regulators of mitochondrial fusion and fission-in our isoproterenol (ISO)-induced heart failure model, ultimately decreasing the severity of heart failure...
2017: PloS One
https://www.readbyqxmd.com/read/28379197/abnormalities-of-mitochondrial-dynamics-in-neurodegenerative-diseases
#15
REVIEW
Ju Gao, Luwen Wang, Jingyi Liu, Fei Xie, Bo Su, Xinglong Wang
Neurodegenerative diseases are incurable and devastating neurological disorders characterized by the progressive loss of the structure and function of neurons in the central nervous system or peripheral nervous system. Mitochondria, organelles found in most eukaryotic cells, are essential for neuronal survival and are involved in a number of neuronal functions. Mitochondrial dysfunction has long been demonstrated as a common prominent early pathological feature of a variety of common neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD)...
April 5, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28372543/giardia-intestinalis-mitosomes-undergo-synchronized-fission-but-not-fusion-and-are-constitutively-associated-with-the-endoplasmic-reticulum
#16
Luboš Voleman, Vladimíra Najdrová, Ásgeir Ástvaldsson, Pavla Tůmová, Elin Einarsson, Zdeněk Švindrych, Guy M Hagen, Jan Tachezy, Staffan G Svärd, Pavel Doležal
BACKGROUND: Mitochondria of opisthokonts undergo permanent fission and fusion throughout the cell cycle. Here, we investigated the dynamics of the mitosomes, the simplest forms of mitochondria, in the anaerobic protist parasite Giardia intestinalis, a member of the Excavata supergroup of eukaryotes. The mitosomes have abandoned typical mitochondrial traits such as the mitochondrial genome and aerobic respiration and their single role known to date is the formation of iron-sulfur clusters...
April 3, 2017: BMC Biology
https://www.readbyqxmd.com/read/28367907/high-resolution-profiles-of-gene-expression-and-dna-methylation-highlight-mitochondrial-modifications-during-early-embryonic-development
#17
Likun Ren, Chao Zhang, Li Tao, Jing Hao, Kun Tan, Kai Miao, Yong Yu, Linlin Sui, Zhonghong Wu, Jianhui Tian, Lei An
Well-organized mitochondrial functions and dynamics are critical for early embryonic development and are operated via a large number of mitochondria-related genes (MtGs) encoded by both the nuclear and the mitochondrial genome. However, the mechanisms underlying mitochondrial modifications during the critical window between blastocyst implantation and postimplantation organogenesis are poorly understood. Herein, we performed high-resolution dynamic profiling of MtGs to acquire a more detailed understanding of mitochondrial modifications during early development...
March 31, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28358017/electron-tomographic-analysis-reveals-ultrastructural-features-of-mitochondrial-cristae-architecture-which-reflect-energetic-state-and-aging
#18
Yi-Fan Jiang, Shao-Syuan Lin, Jing-Min Chen, Han-Zen Tsai, Tao-Shih Hsieh, Chi-Yu Fu
Within mitochondria, the ability to produce energy relies upon the architectural hallmarks of double membranes and cristae invaginations. Herein, we describe novel features of mitochondrial cristae structure, which correspond to the energetic state of the organelle. In concordance with high-energy demand, mitochondria of Drosophila indirect flight muscle exhibited extensive intra-mitochondrial membrane switches between densely packed lamellar cristae that resulted in a spiral-like cristae network and allowed for bidirectional matrix confluency...
March 30, 2017: Scientific Reports
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/28350990/the-putative-drp1-inhibitor-mdivi-1-is-a-reversible-mitochondrial-complex-i-inhibitor-that-modulates-reactive-oxygen-species
#20
Evan A Bordt, Pascaline Clerc, Brian A Roelofs, Andrew J Saladino, László Tretter, Vera Adam-Vizi, Edward Cherok, Ahmed Khalil, Nagendra Yadava, Shealinna X Ge, T Chase Francis, Nolan W Kennedy, Lora K Picton, Tanya Kumar, Sruti Uppuluri, Alexandrea M Miller, Kie Itoh, Mariusz Karbowski, Hiromi Sesaki, R Blake Hill, Brian M Polster
Mitochondrial fission mediated by the GTPase dynamin-related protein 1 (Drp1) is an attractive drug target in numerous maladies that range from heart disease to neurodegenerative disorders. The compound mdivi-1 is widely reported to inhibit Drp1-dependent fission, elongate mitochondria, and mitigate brain injury. Here, we show that mdivi-1 reversibly inhibits mitochondrial complex I-dependent O2 consumption and reverse electron transfer-mediated reactive oxygen species (ROS) production at concentrations (e...
March 27, 2017: Developmental Cell
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