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Mitochondria fission

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https://www.readbyqxmd.com/read/29341879/mechanisms-of-mitochondrial-toxicity-of-the-kinase-inhibitors-ponatinib-regorafenib-and-sorafenib-in-human-hepatic-hepg2-cells
#1
Franziska Paech, Cécile Mingard, David Grünig, Vanessa F Abegg, Jamal Bouitbir, Stephan Krähenbühl
Previous studies have shown that certain kinase inhibitors are mitochondrial toxicants. In the current investigation, we determined the mechanisms of mitochondrial impairment by the kinase inhibitors ponatinib, regorafenib, and sorafenib in more detail. In HepG2 cells cultured in galactose and exposed for 24 hours, all three kinase inhibitors investigated depleted the cellular ATP pools at lower concentrations than cytotoxicity occurred, compatible with mitochondrial toxicity. The kinase inhibitors impaired the activity of different complexes of the respiratory chain in HepG2 cells exposed to the toxicants for 24 hours and in isolated mouse liver mitochondria exposed acutely...
January 13, 2018: Toxicology
https://www.readbyqxmd.com/read/29340618/mitochondrial-toxicity
#2
Joel N Meyer, Jessica H Hartman, Danielle F Mello
Recent decades have seen a rapid increase in reported toxic effects of drugs and pollutants on mitochondria. Researchers have also documented many genetic differences leading to mitochondrial diseases, currently reported to affect ∼1 person in 4,300, creating a large number of potential gene-environment interactions in mitochondrial toxicity. We briefly review this history, and then highlight cutting-edge areas of mitochondrial research including the role of mitochondrial reactive oxygen species in signaling; increased understanding of fundamental biological processes involved in mitochondrial homeostasis (DNA maintenance and mutagenesis, mitochondrial stress response pathways, fusion and fission, autophagy and biogenesis, and exocytosis); systemic effects resulting from mitochondrial stresses in specific cell types; mitochondrial involvement in immune function; the growing evidence of long-term effects of mitochondrial toxicity; mitochondrial-epigenetic cross-talk; and newer approaches to test chemicals for mitochondrial toxicity...
January 11, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29339557/chronic-dietary-creatine-enhances-hippocampal-dependent-spatial-memory-bioenergetics-and-levels-of-plasticity-related-proteins-associated-with-nf-%C3%AE%C2%BAb
#3
Wanda M Snow, Chris Cadonic, Claudia Cortes-Perez, Subir K Roy Chowdhury, Jelena Djordjevic, Ella Thomson, Michael J Bernstein, Miyoung Suh, Paul Fernyhough, Benedict C Albensi
The brain has a high demand for energy, of which creatine (Cr) is an important regulator. Studies document neurocognitive benefits of oral Cr in mammals, yet little is known regarding their physiological basis. This study investigated the effects of Cr supplementation (3%, w/w) on hippocampal function in male C57BL/6 mice, including spatial learning and memory in the Morris water maze and oxygen consumption rates from isolated mitochondria in real time. Levels of transcription factors and related proteins (CREB, Egr1, and IκB to indicate NF-κB activity), proteins implicated in cognition (CaMKII, PSD-95, and Egr2), and mitochondrial proteins (electron transport chain Complex I, mitochondrial fission protein Drp1) were probed with Western blotting...
February 2018: Learning & Memory
https://www.readbyqxmd.com/read/29337889/reactive-oxygen-species-and-mitochondrial-dynamics-the-yin-and-yang-of-mitochondrial-dysfunction-and-cancer-progression
#4
REVIEW
Jan Ježek, Katrina F Cooper, Randy Strich
Mitochondria are organelles with a highly dynamic ultrastructure maintained by a delicate equilibrium between its fission and fusion rates. Understanding the factors influencing this balance is important as perturbations to mitochondrial dynamics can result in pathological states. As a terminal site of nutrient oxidation for the cell, mitochondrial powerhouses harness energy in the form of ATP in a process driven by the electron transport chain. Contemporaneously, electrons translocated within the electron transport chain undergo spontaneous side reactions with oxygen, giving rise to superoxide and a variety of other downstream reactive oxygen species (ROS)...
January 16, 2018: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29334105/specific-labeling-of-mitochondria-of-chlamydomonas-with-cationic-helicene-fluorophores
#5
Christoph Bauer, Romain Duwald, Geraldine Maria Labrador, Simon Pascal, Pau Moneva Lorente, Johann Bosson, Jérôme Lacour, Jean-David Rochaix
Twelve cationic helicenes and one triangulene were tested for the specific labeling of mitochondria from algal cells. Octyl ester derivative 5 readily penetrates algal cells and gives rise to clear fluorescence patterns when it is used at concentrations in the μM range. Under these conditions, cell structures are well preserved and cell survival is not compromised. Cationic helicene compounds such as 5 provide new useful tools for examining the mitochondrial network and its dynamics including fission and fusion events...
January 15, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29321664/mitochondrial-fission-and-mitophagy-depend-on-cofilin-mediated-actin-depolymerization-activity-at-the-mitochondrial-fission-site
#6
Guo-Bing Li, Hong-Wei Zhang, Ruo-Qiu Fu, Xiao-Ye Hu, Lei Liu, Yu-Nong Li, Yan-Xia Liu, Xin Liu, Jin-Jiao Hu, Qin Deng, Qing-Song Luo, Rong Zhang, Ning Gao
Mitochondria fission and mitophagy are fundamentally crucial to cellular physiology and play important roles in cancer progression. Developing a comprehensive understanding of the molecular mechanism underlying mitochondrial fission and mitophagy will provide novel strategies for cancer prevention and treatment. Actin has been shown to participate in mitochondrial fission and mitophagy regulation. Cofilin is best known as an actin-depolymerizing factor. However, the molecular mechanism by which cofilin regulates mitochondrial fission and mitophagy remains largely unknown...
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29321618/uncoupled-mitochondria-quickly-shorten-along-their-long-axis-to-form-indented-spheroids-instead-of-rings-in-a-fission-independent-manner
#7
Yoshihiro Miyazono, Shingo Hirashima, Naotada Ishihara, Jingo Kusukawa, Kei-Ichiro Nakamura, Keisuke Ohta
Loss of mitochondrial membrane potential (ΔΨm) triggers dramatic structural changes in mitochondria from a tubular to globular shape, referred to as mitochondrial fragmentation; the resulting globular mitochondria are called swelled or ring/doughnut mitochondria. We evaluated the early period of structural changes during the ΔΨm loss-induced transformation after carbonyl cyanide m-chlorophenyl hydrazine (CCCP) administration using a newly developed correlative microscopic method combined with fluorescence microscopic live imaging and volume electron microscopy...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321534/mitochondrial-network-complexity-emerges-from-fission-fusion-dynamics
#8
Nahuel Zamponi, Emiliano Zamponi, Sergio A Cannas, Orlando V Billoni, Pablo R Helguera, Dante R Chialvo
Mitochondrial networks exhibit a variety of complex behaviors, including coordinated cell-wide oscillations of energy states as well as a phase transition (depolarization) in response to oxidative stress. Since functional and structural properties are often interwinded, here we characterized the structure of mitochondrial networks in mouse embryonic fibroblasts using network tools and percolation theory. Subsequently we perturbed the system either by promoting the fusion of mitochondrial segments or by inducing mitochondrial fission...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29316789/super-resolution-monitoring-of-mitochondrial-dynamics-upon-time-gated-photo-triggered-release-of-nitric-oxide
#9
Haihong He, Zhiwei Ye, Yi Xiao, Wei Yang, Xuhong Qian, Youjun Yang
Nitric oxide (NO) potentially plays a regulatory role in mitochondrial fusion and fission, which are vital to cell survival and implicated in health, disease and ageing. Molecular tools facilitating study of the interrelationship between NO and mito-chondrial dynamics are in need. We have recently developed a novel NO donor (NOD550). Upon photo-activation, NOD550 decomposes to release two NO molecules and a fluorophore. The NO release could be spatially mapped with sub-diffraction resolution and with a temporal resolution of 10 s...
January 10, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29316654/exercise-and-mitochondrial-dynamics-keeping-in-shape-with-ros-and-ampk
#10
REVIEW
Adam J Trewin, Brandon J Berry, Andrew P Wojtovich
Exercise is a robust stimulus for mitochondrial adaptations in skeletal muscle which consequently plays a central role in enhancing metabolic health. Despite this, the precise molecular events that underpin these beneficial effects remain elusive. In this review, we discuss molecular signals generated during exercise leading to altered mitochondrial morphology and dynamics. In particular, we focus on the interdependence between reactive oxygen species (ROS) and redox homeostasis, the sensing of cellular bioenergetic status via 5' adenosine monophosphate (AMP)-activated protein kinase (AMPK), and the regulation of mitochondrial fission and fusion...
January 6, 2018: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29313986/protein-kinase-d-activation-induces-mitochondrial-fragmentation-and-dysfunction-in-cardiomyocytes
#11
Bong Sook Jhun, Jin O-Uchi, Stephanie M Adaniya, Tomas J Mancini, Jessica L Cao, Michelle E King, Amy K Landi, Hanley Ma, Milla Shin, Donqin Yang, Xiaole Xu, Yisang Yoon, Gaurav Choudhary, Richard T Clements, Ulrike Mende, Shey-Shing Sheu
Regulation of mitochondrial morphology is crucial for the maintenance of physiological functions in many cell types including cardiomyocytes. Small and fragmented mitochondria are frequently observed in pathological condition, but it is still unclear which cardiac signalling pathway is responsible for regulating the abnormal mitochondrial morphology in cardiomyocytes. Here we demonstrate that a downstream kinase of Gq -protein coupled receptor (Gq PCR) signalling, protein kinase D (PKD), mediates pathophysiological modifications in mitochondrial morphology and function, which consequently contribute to the activation of apoptotic signalling...
January 5, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29307555/vps13d-encodes-a-ubiquitin-binding-protein-that-is-required-for-the-regulation-of-mitochondrial-size-and-clearance
#12
Allyson L Anding, Chunxin Wang, Tsun-Kai Chang, Danielle A Sliter, Christine M Powers, Kay Hofmann, Richard J Youle, Eric H Baehrecke
The clearance of mitochondria by autophagy, mitophagy, is important for cell and organism health [1], and known to be regulated by ubiquitin. During Drosophila intestine development, cells undergo a dramatic reduction in cell size and clearance of mitochondria that depends on autophagy, the E1 ubiquitin-activating enzyme Uba1, and ubiquitin [2]. Here we screen a collection of putative ubiquitin-binding domain-encoding genes for cell size reduction and autophagy phenotypes. We identify the endosomal sorting complex required for transport (ESCRT) components TSG101 and Vps36, as well as the novel gene Vps13D...
December 30, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29306791/empagliflozin-rescues-diabetic-myocardial-microvascular-injury-via-ampk-mediated-inhibition-of-mitochondrial-fission
#13
Hao Zhou, Shuyi Wang, Pingjun Zhu, Shunying Hu, Yundai Chen, Jun Ren
Impaired cardiac microvascular function contributes to diabetic cardiovascular complications although effective therapy remains elusive. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor recently approved for treatment of type 2 diabetes, promotes glycosuria excretion and offers cardioprotective actions beyond its glucose-lowering effects. This study was designed to evaluate the effect of empagliflozin on cardiac microvascular injury in diabetes and the underlying mechanism involved with a focus on mitochondria...
December 30, 2017: Redox Biology
https://www.readbyqxmd.com/read/29290987/icg-001-affects-drp1-activity-and-er-stress-correlative-with-its-anti-proliferative-effect
#14
Heidi Zinecker, Djamila Ouaret, Daniel Ebner, Moritz M Gaidt, Steve Taylor, Anna Aulicino, Marta Jagielowicz, Veit Hornung, Alison Simmons
Mitochondria form a highly dynamic network driven by opposing scission and fusion events. DRP1 is an essential modulator of mitochondrial fission and dynamics within mammalian cells. Its fission activity is regulated by posttranslational modifications such as activating phosphorylation at serine 616. DRP1 activity has recently been implicated as being dysregulated in numerous human disorders such as cancer and neurodegenerative diseases. Here we describe the development of a cell-based screening assay to detect DRP1 activation...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29288207/newly-generated-cd4-t-cells-acquire-metabolic-quiescence-after-thymic-egress
#15
Shusong Zhang, Xinwei Zhang, Ke Wang, Xi Xu, Mingyang Li, Jun Zhang, Yan Zhang, Jie Hao, Xiuyuan Sun, Yingyu Chen, Xiaohui Liu, Yingjun Chang, Rong Jin, Hounan Wu, Qing Ge
Mature naive T cells circulate through the secondary lymphoid organs in an actively enforced quiescent state. Impaired cell survival and cell functions could be found when T cells have defects in quiescence. One of the key features of T cell quiescence is low basal metabolic activity. It remains unclear at which developmental stage T cells acquire this metabolic quiescence. We compared mitochondria among CD4 single-positive (SP) T cells in the thymus, CD4+ recent thymic emigrants (RTEs), and mature naive T cells in the periphery...
December 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29278362/intra-and-intercellular-quality-control-mechanisms-of-mitochondria
#16
REVIEW
Yoshimitsu Kiriyama, Hiromi Nochi
Mitochondria function to generate ATP and also play important roles in cellular homeostasis, signaling, apoptosis, autophagy, and metabolism. The loss of mitochondrial function results in cell death and various types of diseases. Therefore, quality control of mitochondria via intra- and intercellular pathways is crucial. Intracellular quality control consists of biogenesis, fusion and fission, and degradation of mitochondria in the cell, whereas intercellular quality control involves tunneling nanotubes and extracellular vesicles...
December 26, 2017: Cells
https://www.readbyqxmd.com/read/29275149/mitochondrial-networking-in-human-blood-cells-with-application-in-acute-care-illnesses
#17
David H Jang, John C Greenwood, Shawn Owiredu, Abhay Ranganathan, David M Eckmann
Mitochondria are dynamic organelles that adapt in response to environmental stresses or mutations. Dynamic processes involving mitochondria include their locomotion within cells and fusion and fission events in which mitochondrial join together or split apart. Various imaging strategies have been utilized to track mitochondrial dynamics. One common limitation of most of the methods available is that the time required to perform the technique and analyze the results prohibits application to clinical diagnosis and therapy...
December 21, 2017: Mitochondrion
https://www.readbyqxmd.com/read/29261068/expression-of-a-t39n-mutant-rab32-protein-arrests-mitochondria-movement-within-neurites-of-differentiated-sh-sy5y-cells
#18
Jonas Rybnicek, Samira Samtleben, Maria Sol Herrera-Cruz, Thomas Simmen
We have shown that multiple sclerosis (MS) and endoplasmic reticulum (ER) stress induce Rab32, an ER/mitochondria-localized small GTPase. High levels of both dominant-active (Q85L) or dominant-inactive (T39N) Rab32 are toxic to neurons. While Rab32Q85L interacts with its effector Drp1 to promote mitochondria fission, it is unclear how Rab32T39N could result as toxic to neurons. Given the perinuclear clustering of mitochondria observed upon transfection of inactive Rab32, we hypothesized Rab32T39N could stall mitochondria within neurites...
December 20, 2017: Small GTPases
https://www.readbyqxmd.com/read/29259094/er-mitochondria-contacts-actin-dynamics-at-the-er-control-mitochondrial-fission-via-calcium-release
#19
Janos Steffen, Carla M Koehler
The formin-like protein INF2 is an important player in the polymerization of actin filaments. In this issue, Chakrabarti et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201709111) demonstrate that INF2 mediates actin polymerization at the endoplasmic reticulum (ER), resulting in increased ER-mitochondria contacts, calcium uptake by mitochondria, and mitochondrial division.
December 19, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29245958/apelin-protects-against-myocardial-ischemic-injury-by-inhibiting-dynamin-related-protein-1
#20
Wei Xu, Hongwei Yu, Ruixue Ma, Lina Ma, Qiushuang Liu, Huitong Shan, Chengyu Wu, Rong Zhang, Yuhong Zhou, Hongli Shan
It is known that dynamin-related protein 1 (Drp1)-mediated mitochondrial fission plays an important role in ischemic injury of myocardial infarction (MI). Apelin, an endogenous ligand for Apelin receptor, acts as a key modulator of cardiovascular diseases. Here, we examined the effects of Apelin on MI injury and underlying mechanisms. Adult male C57BL/6J mice were treated with Apelin for 4 weeks and then subjected coronary artery ligation (LAD) to induce MI and the protective effects of Apelin on MI injury were evaluated at 6 h post LAD...
November 21, 2017: Oncotarget
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