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https://www.readbyqxmd.com/read/29894679/lrrk2-and-mitochondria-recent-advances-and-current-views
#1
Alpana Singh, Lianteng Zhi, Hui Zhang
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene account for most common causes of familial and sporadic Parkinson's disease (PD) and are one of the strongest genetic risk factors in sporadic PD. Pathways implicated in LRRK2-dependent neurodegeneration include cytoskeletal dynamics, vesicular trafficking, autophagy, mitochondria, and calcium homeostasis. However, the exact molecular mechanisms still need to be elucidated. Both genetic and environmental causes of PD have highlighted the importance of mitochondrial dysfunction in the pathogenesis of PD...
June 9, 2018: Brain Research
https://www.readbyqxmd.com/read/29875778/mu-loc-a-machine-learning-method-for-predicting-mitochondrially-localized-proteins-in-plants
#2
Ning Zhang, R S P Rao, Fernanda Salvato, Jesper F Havelund, Ian M Møller, Jay J Thelen, Dong Xu
Targeting and translocation of proteins to the appropriate subcellular compartments are crucial for cell organization and function. Newly synthesized proteins are transported to mitochondria with the assistance of complex targeting sequences containing either an N-terminal pre-sequence or a multitude of internal signals. Compared with experimental approaches, computational predictions provide an efficient way to infer subcellular localization of a protein. However, it is still challenging to predict plant mitochondrially localized proteins accurately due to various limitations...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29872690/mitochondrial-dysfunction-within-the-synapses-of-substantia-nigra-neurons-in-parkinson-s-disease
#3
Amy K Reeve, John P Grady, Eve M Cosgrave, Emma Bennison, Chun Chen, Philippa D Hepplewhite, Christopher M Morris
Mitochondrial dysfunction within the cell bodies of substantia nigra neurons is prominent in both ageing and Parkinson's disease. The loss of dopaminergic substantia nigra neurons in Parkinson's disease is associated with loss of synapses within the striatum, and this may precede neuronal loss. We investigated whether mitochondrial changes previously reported within substantia nigra neurons were also seen within the synapses and axons of these neurons. Using high resolution quantitative fluorescence immunohistochemistry we determined mitochondrial density within remaining dopaminergic axons and synapses, and quantified deficiencies of mitochondrial Complex I and Complex IV in these compartments...
2018: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/29808474/prohibitin-is-a-positive-modulator-of-mitochondrial-function-in-pc12-cells-under-oxidative-stress
#4
Corey J Anderson, Anja Kahl, Liping Qian, Anna Stepanova, Anatoly Starkov, Giovanni Manfredi, Costantino Iadecola, Ping Zhou
Prohibitin (PHB) is a ubiquitously expressed and evolutionarily conserved mitochondrial protein with multiple functions. We have recently shown that PHB upregulation offers robust protection against neuronal injury in models of cerebral ischemia in vitro and in vivo, but the mechanism by which PHB affords neuroprotection remains to be elucidated. Here, we manipulated PHB expression in PC12 neural cells to investigate its impact on mitochondrial function and the mechanisms whereby it protects cells exposed to oxidative stress...
May 28, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29765861/mitochondrial-metabolism-mediated-regulation-of-adult-neurogenesis
#5
REVIEW
Ruth Beckervordersandforth
The life-long generation of new neurons from radial glia-like neural stem cells (NSCs) is achieved through a stereotypic developmental sequence that requires precise regulatory mechanisms to prevent exhaustion or uncontrolled growth of the stem cell pool. Cellular metabolism is the new kid on the block of adult neurogenesis research and the identity of stage-specific metabolic programs and their impact on neurogenesis turns out to be an emerging research topic in the field. Mitochondrial metabolism is best known for energy production but it contains a great deal more...
November 9, 2017: Brain Plasticity
https://www.readbyqxmd.com/read/29762232/modified-exosomes-reduce-apoptosis-and-ameliorate-neural-deficits-induced-by-traumatic-brain-injury
#6
Bo Wang, Shuangshuang Han
Apoptosis contributes to the pathogenesis of traumatic brain injury (TBI). Engineered exosomes incorporated with therapeutic nuclear acids have been explored for gene therapy for human diseases. The current study sought to investigate the effect of modified exosome-containing plasmids expressing B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X-protein (Bax) shRNA on apoptosis and neural functions after TBI. C57BL/6J mice were subjected to controlled cortical impact injury and were treated with the modified exosomes...
May 11, 2018: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
https://www.readbyqxmd.com/read/29694499/deformation-of-mitochondrial-cristae-in-human-neural-progenitor-cells-exposed-to-valproic-acid
#7
Rodrigo M DA Costa, Karina Karmirian, Stevens K Rehen
Neural development represents a dynamic process where mitochondrial integrity is decisive for neuronal activity. Structural changes in these organelles may be related to neurological disorders. Valproic acid (VPA) is an anticonvulsive drug commonly used for epilepsy treatment and its use is associated to increased risk of neuropsychiatric disorders. Recently we showed changes in shape and membrane potential in mitochondria from human neural progenitor cells (NPCs) exposed to VPA (da Costa et al. 2015). Here, we applied transmission electron microscopy and electron tomography to evaluate mitochondrial damage caused by VPA in NPCs...
April 23, 2018: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/29669222/a-mitochondrial-delicacy-dynamin-related-protein-1-and-mitochondrial-dynamics
#8
Mason T Breitzig, Matthew D Alleyn, Richard F Lockey, Narasaiah Kolliputi
The constant physiological flux of mitochondrial fission and fusion is inextricably tied to the maintenance of cellular bioenergetics and the fluidity of mitochondrial networks. Yet, the intricacies of this dynamic duo remain unclear in diseases that encompass mitochondrial dysregulation. Particularly, the role of the GTPase fission protein dynamin-related protein 1 (Drp1) is of profound interest. Studies have identified that Drp1 participates in complex signaling pathways, suggesting that the function of mitochondria in pathophysiology may extend far beyond energetics alone...
April 18, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29666258/formate-rescues-neural-tube-defects-caused-by-mutations-in-slc25a32
#9
Jimi Kim, Yunping Lei, Jin Guo, Sung-Eun Kim, Bogdan J Wlodarczyk, Robert M Cabrera, Ying Linda Lin, Torbjorn K Nilsson, Ting Zhang, Aiguo Ren, Linlin Wang, Zhengwei Yuan, Yu-Fang Zheng, Hong-Yan Wang, Richard H Finnell
Periconceptional folic acid (FA) supplementation significantly reduces the prevalence of neural tube defects (NTDs). Unfortunately, some NTDs are FA resistant, and as such, NTDs remain a global public health concern. Previous studies have identified SLC25A32 as a mitochondrial folate transporter (MFT), which is capable of transferring tetrahydrofolate (THF) from cellular cytoplasm to the mitochondria in vitro. Herein, we show that gene trap inactivation of Slc25a32 ( Mft ) in mice induces NTDs that are folate (5-methyltetrahydrofolate, 5-mTHF) resistant yet are preventable by formate supplementation...
May 1, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29658943/deep-learning-massively-accelerates-super-resolution-localization-microscopy
#10
Wei Ouyang, Andrey Aristov, Mickaël Lelek, Xian Hao, Christophe Zimmer
The speed of super-resolution microscopy methods based on single-molecule localization, for example, PALM and STORM, is limited by the need to record many thousands of frames with a small number of observed molecules in each. Here, we present ANNA-PALM, a computational strategy that uses artificial neural networks to reconstruct super-resolution views from sparse, rapidly acquired localization images and/or widefield images. Simulations and experimental imaging of microtubules, nuclear pores, and mitochondria show that high-quality, super-resolution images can be reconstructed from up to two orders of magnitude fewer frames than usually needed, without compromising spatial resolution...
June 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29615062/kars-related-diseases-progressive-leukoencephalopathy-with-brainstem-and-spinal-cord-calcifications-as-new-phenotype-and-a-review-of-literature
#11
Anna Ardissone, Davide Tonduti, Andrea Legati, Eleonora Lamantea, Rita Barone, Imen Dorboz, Odile Boespflug-Tanguy, Gabriella Nebbia, Marco Maggioni, Barbara Garavaglia, Isabella Moroni, Laura Farina, Anna Pichiecchio, Simona Orcesi, Luisa Chiapparini, Daniele Ghezzi
BACKGROUND: KARS encodes lysyl- transfer ribonucleic acid (tRNA) synthetase, which catalyzes the aminoacylation of tRNA-Lys in the cytoplasm and mitochondria. Eleven families/sporadic patients and 16 different mutations in KARS have been reported to date. The associated clinical phenotype is heterogeneous ranging from early onset encephalopathy to isolated peripheral neuropathy or nonsyndromic hearing impairment. Recently additional presentations including leukoencephalopathy as predominant cerebral involvement or cardiomyopathy, isolated or associated with muscular and cerebral involvement, have been reported...
April 4, 2018: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/29563994/shikonin-induces-mitochondria-mediated-apoptosis-and-attenuates-epithelial-mesenchymal-transition-in-cisplatin-resistant-human-ovarian-cancer-cells
#12
Kristina Shilnikova, Mei Jing Piao, Kyoung Ah Kang, Yea Seong Ryu, Jeong Eon Park, Yu Jae Hyun, Ao Xuan Zhen, Yong Joo Jeong, Uhee Jung, In Gyu Kim, Jin Won Hyun
Cisplatin-based chemotherapy often results in the development of chemoresistance when used to treat ovarian cancer, which is difficult to overcome. The present study investigated the cytotoxic and anti-migratory effects of shikonin, a naphthoquinone compound, on cisplatin-resistant human ovarian cancer A2780 cells (A2780-CR). Shikonin had a potent dose-dependent cytotoxic effect on A2780-CR cells, with 9 µM shikonin treatment reducing A2780-CR cell viability by 50%, validate using an MTT assay. Shikonin induced apoptosis, as evidenced by the increased number of apoptotic bodies, following staining with Hoechst 33342, and terminal deoxynucleotidyl cell transferase dUTP nick end labeling-positive cells following treatment...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29562677/miro1-enhances-mitochondria-transfer-from-multipotent-mesenchymal-stem-cells-mmsc-to-neural-cells-and-improves-the-efficacy-of-cell-recovery
#13
Valentina A Babenko, Denis N Silachev, Vasily A Popkov, Ljubava D Zorova, Irina B Pevzner, Egor Y Plotnikov, Gennady T Sukhikh, Dmitry B Zorov
A recently discovered key role of reactive oxygen species (ROS) in mitochondrial traffic has opened a wide alley for studying the interactions between cells, including stem cells. Since its discovery in 2006, intercellular mitochondria transport has been intensively studied in different cellular models as a basis for cell therapy, since the potential of replacing malfunctioning organelles appears to be very promising. In this study, we explored the transfer of mitochondria from multipotent mesenchymal stem cells (MMSC) to neural cells and analyzed its efficacy under normal conditions and upon induction of mitochondrial damage...
March 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29531533/metabolic-heterogeneity-evidenced-by-mrs-among-patient-derived-glioblastoma-multiforme-stem-like-cells-accounts-for-cell-clustering-and-different-responses-to-drugs
#14
Sveva Grande, Alessandra Palma, Lucia Ricci-Vitiani, Anna Maria Luciani, Mariachiara Buccarelli, Mauro Biffoni, Agnese Molinari, Annarica Calcabrini, Emanuela D'Amore, Laura Guidoni, Roberto Pallini, Vincenza Viti, Antonella Rosi
Clustering of patient-derived glioma stem-like cells (GSCs) through unsupervised analysis of metabolites detected by magnetic resonance spectroscopy (MRS) evidenced three subgroups, namely clusters 1a and 1b, with high intergroup similarity and neural fingerprints, and cluster 2, with a metabolism typical of commercial tumor lines. In addition, subclones generated by the same GSC line showed different metabolic phenotypes. Aerobic glycolysis prevailed in cluster 2 cells as demonstrated by higher lactate production compared to cluster 1 cells...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29513101/rip140-pgc-1%C3%AE-axis-involved-in-vitamin-a-induced-neural-differentiation-by-increasing-mitochondrial-function
#15
Qing Mu, Weidong Yu, Shuying Zheng, Hongxia Shi, Mei Li, Jie Sun, Di Wang, Xiaoli Hou, Ling Liu, Xinjuan Wang, Zhuran Zhao, Rong Liang, Xue Zhang, Wei Dong, Chaomei Zeng, Jingzhu Guo
Vitamin A deficiency and mitochondrial dysfunction are both associated with neural differentiation-related disorders, such as Alzheimer's disease (AD) and Down syndrome (DS). The mechanism of vitamin A-induced neural differentiation and the notion that vitamin A can regulate the morphology and function of mitochondria in its induction of neural differentiation through the RIP140/PGC-1α axis are unclear. The aim of this study was to investigate the roles and underlying mechanisms of RIP140/PGC-1α axis in vitamin A-induced neural differentiation...
March 7, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29496782/brain-mitochondrial-bioenergetics-change-with-rapid-and-prolonged-shifts-in-aggression-in-the-honey-bee-apis-mellifera
#16
Clare C Rittschof, Hemendra J Vekaria, Joseph H Palmer, Patrick G Sullivan
Neuronal function demands high-level energy production, and as such, a decline in mitochondrial respiration characterizes brain injury and disease. A growing number of studies, however, link brain mitochondrial function to behavioral modulation in non-diseased contexts. In the honey bee, we show for the first time that an acute social interaction, which invokes an aggressive response, may also cause a rapid decline in brain mitochondrial bioenergetics. The degree and speed of this decline has only been previously observed in the context of brain injury...
April 25, 2018: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29495951/mitochondrial-dysfunction-maternal-protein-restriction-as-a-trigger-of-reactive-species-overproduction-and-brainstem-energy-failure-in-male-offspring-brainstem
#17
D J S Ferreira, A A Pedroza, G R F Braz, M P Fernandes, C J Lagranha
Mitochondria are important organelles in eukaryotic organisms, wherein their capacity to produce energy vary among the tissues depending upon the amounts of oxygen consumed. Part of the oxygen consumed during ATP generation produces reactive oxygen species, which if not efficiently removed can trigger a systemic damage to molecular compounds characterized as oxidative stress. Several studies have demonstrated that mitochondrial dysfunction and oxidative stress in the central nervous system (CNS) are related to a plethora of neural disorders...
March 1, 2018: Nutritional Neuroscience
https://www.readbyqxmd.com/read/29466734/pharmacological-inhibition-of-necroptosis-protects-from-dopaminergic-neuronal-cell-death-in-parkinson-s-disease-models
#18
Angelo Iannielli, Simone Bido, Lucrezia Folladori, Alice Segnali, Cinzia Cancellieri, Alessandra Maresca, Luca Massimino, Alicia Rubio, Giuseppe Morabito, Leonardo Caporali, Francesca Tagliavini, Olimpia Musumeci, Giuliana Gregato, Erwan Bezard, Valerio Carelli, Valeria Tiranti, Vania Broccoli
Dysfunctions in mitochondrial dynamics and metabolism are common pathological processes associated with Parkinson's disease (PD). It was recently shown that an inherited form of PD and dementia is caused by mutations in the OPA1 gene, which encodes for a key player in mitochondrial fusion and structure. iPSC-derived neural cells from these patients exhibited severe mitochondrial fragmentation, respiration impairment, ATP deficits, and heightened oxidative stress. Reconstitution of normal levels of OPA1 in PD-derived neural cells normalized mitochondria morphology and function...
February 20, 2018: Cell Reports
https://www.readbyqxmd.com/read/29453779/mitochondrial-cytochrome-p450-cyp-1b1-is-responsible-for-melatonin-induced-apoptosis-in-neural-cancer-cells
#19
Zhenlong Yu, Xiangge Tian, Yuling Peng, Zheng Sun, Chao Wang, Ning Tang, Bin Li, Yuqing Jian, Wei Wang, Xiaokui Huo, Xiaochi Ma
Melatonin is an endogenous indoleamine with a wide range of biological functions in the various organisms from bacteria to mammals. Evidence indicates that melatonin facilitates apoptosis in cancer cells and enhances the antitumor activity of chemotherapy in animals and clinical studies. However, the melatonin metabolism and the key metabolic targets in cancer cells still remain unknown. In this study, U118 and SH-SY5Y tumor cell lines were used to investigate the metabolic pathways of melatonin in cancer cells...
February 17, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29445135/alteration-in-nerves-and-neurotransmitter-stimulation-of-lacrimal-gland-secretion-in-the-tsp-1-mouse-model-of-aqueous-deficiency-dry-eye
#20
Sumit Bhattacharya, Laura García-Posadas, Robin R Hodges, Helen P Makarenkova, Sharmila Masli, Darlene A Dartt
The purpose of this study is to determine neural, vascular, protein secretion, and cellular signaling changes with disease progression in lacrimal glands of the thrombospondin-1-/- (TSP-1-/- ) mouse model of dry eye compared to C57BL/6 wild-type (WT) mice. Neural innervation was reduced in TSP-1-/- lacrimal glands compared to WT controls, whereas the number of blood vessels was increased. Intracellular Ca2+ stores and the amount of lysosomes, mitochondria, and secretory granules, but not the endoplasmic reticulum, were reduced in TSP-1-/- compared to WT acini at 12 weeks of age...
February 14, 2018: Mucosal Immunology
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