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Mitochondrial disease complex I

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https://www.readbyqxmd.com/read/29779213/differential-toxicity-of-tdp-43-isoforms-depends-on-their-sub-mitochondrial-localization-in-neuronal-cells
#1
Illari Salvatori, Alberto Ferri, Silvia Scaricamazza, Ilaria Giovannelli, Alessia Serrano, Simona Rossi, Nadia D'Ambrosi, Mauro Cozzolino, Andrea Di Giulio, Sandra Moreno, Cristiana Valle, Maria Teresa Carrì
TAR DNA binding protein 43 (TDP-43) is an RNA binding protein and a major component of protein aggregates found in Amyotrophic Lateral Sclerosis and several other neurodegenerative diseases. TDP-43 exists as a full length protein and as two shorter forms of 25 and 35 kDa. Full length mutant TDP-43s found in ALS patients re-localize from the nucleus to the cytoplasm and in part to mitochondria, where they exert a toxic role associated with neurodegeneration. However, induction of mitochondrial damage by TDP-43 fragments is yet to be clarified...
May 20, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29775890/triterpenic-acids-enriched-fraction-from-cyclocarya-paliurus-attenuates-non-alcoholic-fatty-liver-disease-via-improving-oxidative-stress-and-mitochondrial-dysfunction
#2
Meng-Ge Zhao, Xue-Ping Sheng, Ya-Ping Huang, Yi-Ting Wang, Cui-Hua Jiang, Jian Zhang, Zhi-Qi Yin
The effects of triterpenic acids-enriched fraction from Cyclocarya paliurus (CPT) on nonalcoholic fatty liver disease (NAFLD) were investigated using in vivo and in vitro models. In high fat diet-induced Wister rats, CPT significantly increased superoxide dismutase (SOD) activity and glutathione/oxidized glutathione (GSH/GSSG) ratio, reduced malondialdehyde (MDA) and protein carbonyl (PCO) levels. Moreover, CPT restored mitochondrial membrane potential dysfunction, decreased cytochrome P450 enzyme 2E1 (CYP2E1) activity, improved nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-mediated antioxidant enzyme heme oxygenase1 (HO-1) expression...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29773347/lipophilic-methylene-blue-analogues-enhance-mitochondrial-function-and-increase-frataxin-levels-in-a-cellular-model-of-friedreich-s-ataxia
#3
Omar M Khdour, Indrajit Bandyopadhyay, Sandipan Roy Chowdhury, Nishant P Visavadiya, Sidney M Hecht
Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder resulting from reduced expression of the protein frataxin (FXN). Although its function is not fully understood, frataxin appears to help assemble iron sulfur clusters; these are critical for the function of many proteins, including those needed for mitochondrial energy production. Finding ways to increase FXN levels has been a major therapeutic strategy for this disease. Previously, we described a novel series of methylene violet analogues and their structural optimization as potential therapeutic agents for neurodegenerative and mitochondrial disorders...
May 4, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29769317/lysophospholipids-induce-innate-immune-transdifferentiation-of-endothelial-cells-resulting-in-prolonged-endothelial-activation
#4
Xinyuan Li, Luqiao Wang, Pu Fang, Yu Sun, Xiaohua Jiang, Hong Wang, Xiao-Feng Yang
Innate immune cells express danger-associated molecular pattern (DAMP) receptors, T-cell co-stimulation/co-inhibition receptors, and the major histocompatibility complex II (MHC-II). We have recently proposed that endothelial cells can serve as innate immune cells, but the molecular mechanisms involved still await discovery. Here, we investigated whether human aortic endothelial cells (HAECs) could be transdifferentiated into innate immune cells by exposing them to hyperlipidemia-upregulated DAMP molecules, i...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29757522/evidence-of-natural-wolbachia-infections-and-molecular-identification-of-field-populations-of-culex-pipiens-complex-diptera-culicidae-mosquitoes-in-western-turkey
#5
Burçin Morçiçek, Belgin Gocmen Taskin, Ersin Doğaç, Taylan Doğaroğlu, Vatan Taskin
Establishing reliable risk projection information about the distribution pattern of members of the Culex pipiens complex is of particular interest, as these mosquitoes are competent vectors for certain disease-causing pathogens. Wolbachia, a maternally inherited bacterial symbiont, are distributed in various arthropod species and can induce cytoplasmic incompatibility, i.e., reduced egg hatch, in certain crosses. It is being considered as a tool for population control of mosquito disease vectors. The Aegean region is characterized by highly populated, rural, and agricultural areas and is also on the route of the migratory birds...
June 2018: Journal of Vector Ecology: Journal of the Society for Vector Ecology
https://www.readbyqxmd.com/read/29748634/gene-by-environment-interactions-that-disrupt-mitochondrial-homeostasis-cause-neurodegeneration-in-c-elegans-parkinson-s-models
#6
Hanna Kim, Rylee J Perentis, Guy A Caldwell, Kim A Caldwell
Parkinson's disease (PD) is a complex multifactorial disorder where environmental factors interact with genetic susceptibility. Accumulating evidence suggests that mitochondria have a central role in the progression of neurodegeneration in sporadic and/or genetic forms of PD. We previously reported that exposure to a secondary metabolite from the soil bacterium, Streptomyces venezuelae, results in age- and dose-dependent dopaminergic (DA) neurodegeneration in Caenorhabditis elegans and human SH-SY5Y neurons...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29738577/widespread-plant-specialization-in-the-polyphagous-planthopper-hyalesthes-obsoletus-cixiidae-a-major-vector-of-stolbur-phytoplasma-evidence-of-cryptic-speciation
#7
Andrea Kosovac, Jes Johannesen, Oliver Krstić, Milana Mitrović, Tatjana Cvrković, Ivo Toševski, Jelena Jović
The stolbur phytoplasma vector Hyalesthes obsoletus is generally considered as a polyphagous species associated with numerous wild and cultivated plants. However, recent research in southeastern Europe, the distribution centre of H. obsoletus and the area of most stolbur-inflicted crop diseases, points toward specific host-plant associations of the vector, indicating specific vector-based transmission routes. Here, we study the specificity of populations associated with four host-plants using mitochondrial and nuclear genetic markers, and we evaluate the evolution of host-shifts in H...
2018: PloS One
https://www.readbyqxmd.com/read/29732085/discovery-of-the-novel-autophagy-inhibitor-aumitin-that-targets-mitochondrial-complex-i
#8
Lucas Robke, Yushi Futamura, Georgios Konstantinidis, Julian Wilke, Harumi Aono, Zhwan Mahmoud, Nobumoto Watanabe, Yao-Wen Wu, Hiroyuki Osada, Luca Laraia, Herbert Waldmann
Macroautophagy is a conserved eukaryotic process for degradation of cellular components in response to lack of nutrients. It is involved in the development of diseases, notably cancer and neurological disorders including Parkinson's disease. Small molecule autophagy modulators have proven to be valuable tools to dissect and interrogate this crucial metabolic pathway and are in high demand. Phenotypic screening for autophagy inhibitors led to the discovery of the novel autophagy inhibitor aumitin. Target identification and confirmation revealed that aumitin inhibits mitochondrial respiration by targeting complex I...
March 21, 2018: Chemical Science
https://www.readbyqxmd.com/read/29719834/genomic-instabilities-cellular-senescence-and-aging-in-vitro-in-vivo-and-aging-like-human-syndromes
#9
REVIEW
Gabriel Lidzbarsky, Danielle Gutman, Huda Adwan Shekhidem, Lital Sharvit, Gil Atzmon
As average life span and elderly people prevalence in the western world population is gradually increasing, the incidence of age-related diseases such as cancer, heart diseases, diabetes, and dementia is increasing, bearing social and economic consequences worldwide. Understanding the molecular basis of aging-related processes can help extend the organism's health span, i.e., the life period in which the organism is free of chronic diseases or decrease in basic body functions. During the last few decades, immense progress was made in the understanding of major components of aging and healthy aging biology, including genomic instability, telomere attrition, epigenetic changes, proteostasis, nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and intracellular communications...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29718187/mutations-in-coa7-cause-spinocerebellar-ataxia-with-axonal-neuropathy
#10
Yujiro Higuchi, Ryuta Okunushi, Taichi Hara, Akihiro Hashiguchi, Junhui Yuan, Akiko Yoshimura, Kei Murayama, Akira Ohtake, Masahiro Ando, Yu Hiramatsu, Satoshi Ishihara, Hajime Tanabe, Yuji Okamoto, Eiji Matsuura, Takehiro Ueda, Tatsushi Toda, Sumimasa Yamashita, Kenichiro Yamada, Takashi Koide, Hiroaki Yaguchi, Jun Mitsui, Hiroyuki Ishiura, Jun Yoshimura, Koichiro Doi, Shinichi Morishita, Ken Sato, Masanori Nakagawa, Masamitsu Yamaguchi, Shoji Tsuji, Hiroshi Takashima
Several genes related to mitochondrial functions have been identified as causative genes of neuropathy or ataxia. Cytochrome c oxidase assembly factor 7 (COA7) may have a role in assembling mitochondrial respiratory chain complexes that function in oxidative phosphorylation. Here we identified four unrelated patients with recessive mutations in COA7 among a Japanese case series of 1396 patients with Charcot-Marie-Tooth disease (CMT) or other inherited peripheral neuropathies, including complex forms of CMT...
April 27, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29710722/mitochondrial-dysfunction-as-a-predictor-and-driver-of-alzheimer-s-disease-like-pathology-in-oxys-rats
#11
Mikhail A Tyumentsev, Natalia A Stefanova, Natalia A Muraleva, Yulia V Rumyantseva, Elena Kiseleva, Valentin A Vavilin, Nataliya G Kolosova
Growing evidence suggests that mitochondrial dysfunction is an early event in sporadic Alzheimer's disease (AD), but the impact of mitochondrial dysfunction on the transition from healthy aging to AD remains elusive. Here we estimated the influence of mitochondrial dysfunction on the initiation of AD signs in OXYS rats, which simulate key characteristics of sporadic AD. We assessed the mitochondrial ultrastructure of pyramidal neurons of the hippocampus at the age preceding the development (age 20 days), during manifestation (4-5 months), and at the well-pronounced stages (18-24 months) of the AD-like pathology in OXYS rats...
April 27, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29704589/mitochondrial-alterations-in-parkinson-s-disease-human-samples-and-cellular-models
#12
Mara Zilocchi, Giovanna Finzi, Marta Lualdi, Fausto Sessa, Mauro Fasano, Tiziana Alberio
Mitochondrial impairment is one of the most important hallmarks of Parkinson's disease (PD) pathogenesis. In this work, we wanted to verify the molecular basis of altered mitochondrial dynamics and disposal in Substantia nigra specimens of sporadic PD patients, by the comparison with two cellular models of PD. Indeed, SH-SY5Y cells were treated with either dopamine or 1-methyl-4-phenylpyridinium (MPP+ ) in order to highlight the effect of altered dopamine homeostasis and of complex I inhibition, respectively...
April 25, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29702063/mitochondrial-interaction-of-alpha-synuclein-leads-to-irreversible-translocation-and-complex-i-impairment
#13
Jimena H Martínez, Federico Fuentes, Virginia Vanasco, Silvia Alvarez, Agustina Alaimo, Adriana Cassina, Federico Coluccio Leskow, Francisco Velazquez
α-synuclein is involved in both familial and sporadic Parkinson's disease. Although its interaction with mitochondria has been well documented several aspects remains unknown or under debate; such as the specific sub-mitochondrial localization of α-synuclein or the dynamics of the interaction. It has been suggested that α-synuclein could only interact with ER-associated mitochondria. Variety of model systems and experimental conditions makes difficult to compare results and extract definitive conclusions...
April 24, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29700116/comparative-analysis-of-parkinson-s-disease-associated-genes-reveals-altered-survival-and-bioenergetics-of-parkin-deficient-dopamine-neurons-in-mice
#14
Nicolas Giguere, Consiglia Pacelli, Caroline Saumure, Marie-Josee Bourque, Diana Matheoud, Daniel Levesque, Ruth S Slack, David S Park, Louis-Eric Trudeau
Many mutations in genes encoding proteins such as parkin, PTEN-induced putative kinase 1 (PINK1), protein deglycase DJ-1 (DJ-1 or PARK7), leucine-rich repeat kinase 2 (LRRK2), and α-synuclein have been linked to familial forms of Parkinson's disease (PD). The consequences of these mutations, such as altered mitochondrial function and pathological protein aggregation, are starting to be better understood. However, little is known about the mechanisms explaining why alterations in such diverse cellular mechanisms lead to the selective loss of dopamine (DA) neurons in the substantia nigra (SNc) in the brain of individuals with PD...
April 26, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29679893/identification-of-homocysteine-suppressive-mitochondrial-etc-complex-genes-and-tissue-expression-profile-novel-hypothesis-establishment
#15
Ramon Cueto, Lixiao Zhang, Hui Min Shan, Xiao Huang, Xinyuan Li, Ya-Feng Li, Jahaira Lopez, William Y Yang, Muriel Lavallee, Catherine Yu, Yong Ji, Xiaofeng Yang, Hong Wang
Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease (CVD) which has been implicated in matochondrial (Mt) function impairment. In this study, we characterized Hcy metabolism in mouse tissues by using LC-ESI-MS/MS analysis, established tissue expression profiles for 84 nuclear-encoded Mt electron transport chain complex (nMt-ETC-Com) genes in 20 human and 19 mouse tissues by database mining, and modeled the effect of HHcy on Mt-ETC function. Hcy levels were high in mouse kidney/lung/spleen/liver (24-14 nmol/g tissue) but low in brain/heart (~5 nmol/g)...
April 4, 2018: Redox Biology
https://www.readbyqxmd.com/read/29678518/pattern-recognition-receptors-mediate-pro-inflammatory-effects-of-extracellular-mitochondrial-transcription-factor-a-tfam
#16
Stephanie M Schindler, Matthew G Frank, Jessica L Annis, Steven F Maier, Andis Klegeris
Neuroinflammation is a common pathogenic mechanism for a number of neurodegenerative disorders including Alzheimer's and Parkinson's diseases. Microglia, the immune cells of the brain, contribute to the onset and progression of the neuroinflammation observed in these diseases. Microglia become activated and initiate an inflammatory response by interacting with a diverse set of molecules, including the group of endogenous proteins released upon cell damage, termed damage-associated molecular patterns (DAMPs)...
April 17, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29675530/hepatoprotective-activity-of-iridoids-seco-iridoids-and-analog-glycosides-from-gentianaceae-on-hepg2-cells-via-cyp3a4-induction-and-mitochondrial-pathway
#17
Kang Dai, Xue-Jia Yi, Xian-Ju Huang, Azhar Muhammad, Mei Li, Jun Li, Guang-Zhong Yang, Yue Gao
Gentianaceae herb extracts have been widely used as food additives, teas or medicinal remedies for various diseases and disorders of the human body. Herein, the potential effects of iridoids, seco-iridoids and analog glycosides from gentian on acontine-induced hepatotoxicity were investigated in HepG2 cells to obtain metabolic data of drug-biotarget interactions. Molecular docking analysis was performed to assess the binding efficiencies of 53 iridoids, seco-iridoids and analog compounds obtained from 50 gentian species to the active sites of human CYP3A4 enzyme...
April 20, 2018: Food & Function
https://www.readbyqxmd.com/read/29673597/sennoside-a-protects-mitochondrial-structure-and-function-to-improve-high-fat-diet-induced-hepatic-steatosis-by-targeting-vdac1
#18
Jiamei Le, Weiping Jia, Yongning Sun
Mitochondrial dysfunction is mainly associated with high-fat-diet (HFD)-induced hepatic steatosis. Sennoside A (SA), a commonly used clinical stimulant laxative, is reported to improve energy metabolism and insulin resistance. However, the effect and mechanism of SA on HFD-induced hepatic steatosis remain largely unknown. The aim of this study was to determine the effect and mechanism of SA on HFD-induced hepatic steatosis in mice. We examined the liver and body weight of mice to evaluate the physical changes in the liver...
April 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29671021/protective-effect-of-vinpocetine-against-neurotoxicity-of-manganese-in-adult-male-rats
#19
Rania I Nadeem, Hebatalla I Ahmed, Bahia M El-Sayeh
Manganese (Mn) is required for many essential biological processes as well as in the development and functioning of the brain. Extensive accumulation of Mn in the brain may cause central nervous system dysfunction known as manganism, a motor disorder associated with cognitive and neuropsychiatric deficits similar to parkinsonism. Vinpocetine, a synthetic derivative of the alkaloid vincamine, is used to improve the cognitive function in cerebrovascular diseases. It possesses antioxidant and antiinflammatory properties...
April 18, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29660213/role-of-ncor1-in-mitochondrial-function-and-energy-metabolism
#20
REVIEW
Tanes I Lima, Rafael R Valentim, Hygor N Araújo, André G Oliveira, Bianca C Favero, Eveline S Menezes, Rafaela Araújo, Leonardo R Silveira
Mitochondrial number and shape are constantly changing in response to increased energy demands. The ability to synchronize mitochondrial pathways to respond to energy fluctuations within the cell is a central aspect of mammalian homeostasis. This dynamic process depends on the coordinated activation of transcriptional complexes to promote the expression of genes encoding for mitochondrial proteins. Recent evidence has shown that the nuclear corepressor NCoR1 is an essential metabolic switch which acts on oxidative metabolism signaling...
April 16, 2018: Cell Biology International
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