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Mitochondrial plasticity

Dongya Jia, Jun Hyoung Park, Kwang Hwa Jung, Herbert Levine, Benny Abraham Kaipparettu
Aerobic glycolysis, also referred to as the Warburg effect, has been regarded as the dominant metabolic phenotype in cancer cells for a long time. More recently, it has been shown that mitochondria in most tumors are not defective in their ability to carry out oxidative phosphorylation (OXPHOS). Instead, in highly aggressive cancer cells, mitochondrial energy pathways are reprogrammed to meet the challenges of high energy demand, better utilization of available fuels and macromolecular synthesis for rapid cell division and migration...
March 13, 2018: Cells
Fenghua Chen, Jibrin Danladi, Maryam Ardalan, Betina Elfving, Heidi K Müller, Gregers Wegener, Connie Sanchez, Jens R Nyengaard
Background: Preclinical studies have indicated that antidepressant effect of vortioxetine involves increased synaptic plasticity and promotion of spine maturation. Mitochondria dysfunction may contribute to the pathophysiological basis of major depressive disorder. Taking into consideration that vortioxetine increases spine number and dendritic branching in hippocampus CA1 faster than fluoxetine, we hypothesize that new spines induced by vortioxetine can rapidly form functional synapses by mitochondrial support, accompanied by increased brain-derived neurotrophic factor (BDNF)-signaling...
March 5, 2018: International Journal of Neuropsychopharmacology
Cornelius K Donat, Nazanin Mirzaei, Sac-Pharm Tang, Paul Edison, Magdalena Sastre
Deficits in neuronal function and synaptic plasticity in Alzheimer's disease (AD) are believed to be linked to microglial activation. A hallmark of reactive microglia is the upregulation of mitochondrial translocator protein (TSPO) expression. Positron emission tomography (PET) is a nuclear imaging technique that measures the distribution of trace doses of radiolabeled compounds in the body over time. PET imaging using the 2nd generation TSPO tracer [11 C]PBR28 provides an opportunity for accurate visualization and quantification of changes in microglial density in transgenic mouse models of Alzheimer's disease (AD)...
2018: Methods in Molecular Biology
Carola Stockburger, Schamim Eckert, Gunter P Eckert, Kristina Friedland-Leuner, Walter E Müller
Because of the failure of all amyloid-β directed treatment strategies for Alzheimer's disease (AD), the concept of mitochondrial dysfunction as a major pathomechanism of the cognitive decline in aging and AD has received substantial support. Accordingly, improving mitochondrial function as an alternative strategy for new drug development became of increasing interest and many different compounds have been identified which improve mitochondrial function in preclinical in vitro and in vivo experiments. However, very few if any have been investigated in clinical trials, representing a major drawback of the mitochondria directed drug development...
February 28, 2018: Journal of Alzheimer's Disease: JAD
Qiu-Lan Ma, Edmond Teng, Xiaohong Zuo, Mychica Jones, Bruce Teter, Evan Y Zhao, Cansheng Zhu, Tina Bilousova, Karen H Gylys, Liana G Apostolova, Mary Jo LaDu, Mir Ahamed Hossain, Sally A Frautschy, Gregory M Cole
Synaptic neurodegeneration is thought to be an early event initiated by soluble β-amyloid (Aβ) aggregates that closely correlates with cognitive decline in Alzheimer disease (AD). Apolipoprotein ε4 (APOE4) is the most common genetic risk factor for both familial AD (FAD) and sporadic AD; it accelerates Aβ aggregation and selectively impairs glutamate receptor function and synaptic plasticity. However, its molecular mechanisms remain elusive and these synaptic deficits are difficult to monitor. AD- and APOE4-dependent plasma biomarkers have been proposed, but synapse-related plasma biomarkers are lacking...
February 28, 2018: Neurobiology of Disease
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...
March 1, 2018: Journal of Experimental Biology
Rawadee Kumlert, Kittipong Chaisiri, Tippawan Anantatat, Alexandr A Stekolnikov, Serge Morand, Anchana Prasartvit, Benjamin L Makepeace, Sungsit Sungvornyothin, Daniel H Paris
BACKGROUND: Conventional gold standard characterization of chigger mites involves chemical preparation procedures (i.e. specimen clearing) for visualization of morphological features, which however contributes to destruction of the arthropod host DNA and any endosymbiont or pathogen DNA harbored within the specimen. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a novel work flow based on autofluorescence microscopy was developed to enable identification of trombiculid mites to the species level on the basis of morphological traits without any special preparation, while preserving the mite DNA for subsequent genotyping...
2018: PloS One
Krisztina Marosi, Keelin Moehl, Ignacio Navas-Enamorado, Sarah J Mitchell, Yongqing Zhang, Elin Lehrmann, Miguel A Aon, Sonia Cortassa, Kevin G Becker, Mark P Mattson
Evolutionary considerations suggest that the body has been optimized to perform at a high level in the food-deprived state when fatty acids and their ketone metabolites are a major fuel source for muscle cells. Because controlled food deprivation in laboratory animals and intermittent energy restriction in humans is a potent physiologic stimulus for ketosis, we designed a study to determine the impact of intermittent food deprivation during endurance training on performance and to elucidate the underlying cellular and molecular mechanisms...
February 27, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Ana Gutiérrez-Rodríguez, Itziar Bonilla-Del Río, Nagore Puente, Sonia M Gómez-Urquijo, Christine J Fontaine, Jon Egaña-Huguet, Izaskun Elezgarai, Sabine Ruehle, Beat Lutz, Laurie M Robin, Edgar Soria-Gómez, Luigi Bellocchio, Jalindar D Padwal, Mario van der Stelt, Juan Mendizabal-Zubiaga, Leire Reguero, Almudena Ramos, Inmaculada Gerrikagoitia, Giovanni Marsicano, Pedro Grandes
Astroglial type-1 cannabinoid (CB1 ) receptors are involved in synaptic transmission, plasticity and behavior by interfering with the so-called tripartite synapse formed by pre- and post-synaptic neuronal elements and surrounding astrocyte processes. However, little is known concerning the subcellular distribution of astroglial CB1 receptors. In particular, brain CB1 receptors are mostly localized at cells' plasmalemma, but recent evidence indicates their functional presence in mitochondrial membranes. Whether CB1 receptors are present in astroglial mitochondria has remained unknown...
February 26, 2018: Glia
Diane M Sepa-Kishi, Rolando B Ceddia
The white adipose tissue (WAT) exhibits great plasticity and can undergo "browning" and acquire features of the brown adipose tissue (BAT), which takes place following cold exposure, chronic endurance exercise or β3-adrenergic stimulation. WAT that underwent browning is characterized by the presence of "beige" adipocytes, which are morphologically similar to brown adipocytes, express uncoupling protein 1 (UCP1) and are considered thermogenically competent. Thus, inducing a BAT-like phenotype in the WAT could promote energy dissipation within this depot, reducing the availability of substrate that would otherwise be stored in the WAT...
February 21, 2018: Hormone Molecular Biology and Clinical Investigation
Brittany G Durgin, Adam C Straub
Vascular smooth muscle cells (SMC) play a major role in vascular diseases, such as atherosclerosis and hypertension. It has long been established in vitro that contractile SMC can phenotypically switch to function as proliferative and/or migratory cells in response to stimulation by oxidative stress, growth factors, and inflammatory cytokines. Reactive oxygen species (ROS) are oxidative stressors implicated in driving vascular diseases, shifting cell bioenergetics, and increasing SMC proliferation, migration, and apoptosis...
February 20, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Pei-I Tsai, Chin-Hsien Lin, Chung-Han Hsieh, Amanda M Papakyrikos, Min Joo Kim, Valerio Napolioni, Carmen Schoor, Julien Couthouis, Ruey-Meei Wu, Zbigniew K Wszolek, Dominic Winter, Michael D Greicius, Owen A Ross, Xinnan Wang
Mitochondrial crista structure partitions vital cellular reactions and is precisely regulated by diverse cellular signals. Here, we show that, in Drosophila, mitochondrial cristae undergo dynamic remodeling among distinct subcellular regions and the Parkinson's disease (PD)-linked Ser/Thr kinase PINK1 participates in their regulation. Mitochondria increase crista junctions and numbers in selective subcellular areas, and this remodeling requires PINK1 to phosphorylate the inner mitochondrial membrane protein MIC60/mitofilin, which stabilizes MIC60 oligomerization...
February 14, 2018: Molecular Cell
Victor G Gómez-Pineda, Francisco M Torres-Cruz, César I Vivar-Cortés, Elizabeth Hernández-Echeagaray
AIMS: Neurotrophin-3 (NT-3) is expressed in the mouse striatum; however, it is not clear the NT-3 role in striatal physiology. The expression levels of mRNAs and immune localization of the NT-3 protein and its receptor TrkC are altered in the striatum following damage induced by an in vivo treatment with 3-nitropropionic acid (3-NP), a mitochondrial toxin used to mimic the histopathological hallmarks of Huntington's disease (HD). The aim of this study was to evaluate the role of NT-3 on corticostriatal synaptic transmission and its plasticity in both the control and damaged striatum...
February 17, 2018: CNS Neuroscience & Therapeutics
Ricardo A Maselli, Jessica Vázquez, Leah Schrumpf, Juan Arredondo, Marian Lara, Jonathan B Strober, Peter Pytel, Robert L Wollmann, Michael Ferns
BACKGROUND: Monogenic defects of synaptic vesicle (SV) homeostasis have been implicated in many neurologic diseases, including autism, epilepsy, and movement disorders. In addition, abnormal vesicle exocytosis has been associated with several endocrine dysfunctions. METHODS: We report an 11 year old girl with learning disabilities, tremors, ataxia, transient hyperglycemia, and muscle fatigability responsive to albuterol sulfate. Failure of neuromuscular transmission was confirmed by single fiber electromyography...
February 14, 2018: Molecular Genetics & Genomic Medicine
Ashish Kumar, Sagnik Giri, Chandrima Shaha
Differential utilization of metabolites and metabolic plasticity can confer adaptation to cancer cells under metabolic stress. Glutamine is one of the vital and versatile nutrients which cancer cells consume avidly for their proliferation, therefore, mechanisms related to glutamine metabolism has been identified as targets. Recently, SESN2 (sestrin2), a stress inducible protein has been reported to regulate survival in glutamine depleted cancer cells, based on this, we explored if SESN2 could regulate glutamine metabolism during glucose starvation...
February 12, 2018: FEBS Journal
Enxuan Jing, Pragalath Sundararajan, Ishita Deb Majumdar, Suwagmani Hazarika, Samantha Fowler, Angela Szeto, Stephane Gesta, Armando J Mendez, Vivek K Vishnudas, Rangaprasad Sarangarajan, Niven R Narain
Background: Inhibition of Hsp90 has been shown to improve glucose tolerance and insulin sensitivity in mouse models of diabetes. In the present report, the specific isoform Hsp90ab1, was identified as playing a major role in regulating insulin signaling and glucose metabolism. Methods: In a diet-induced obese (DIO) mouse model of diabetes, expression of various Hsp90 isoforms in skeletal tissue was examined. Subsequent experiments characterized the role of Hsp90ab1 isoform in glucose metabolism and insulin signaling in primary human skeletal muscle myoblasts (HSMM) and a DIO mouse model...
2018: Nutrition & Metabolism
Felipe Paredes, Kely Sheldon, Bernard Lassègue, Holly C Williams, Elizabeth A Faidley, Gloria A Benavides, Gloria Torres, Fernanda Sanhueza-Olivares, Samantha M Yeligar, Kathy K Griendling, Victor Darley-Usmar, Alejandra San Martin
Although the addition of the prosthetic group lipoate is essential to the activity of critical mitochondrial catabolic enzymes, its regulation is unknown. Here, we show that lipoylation of the pyruvate dehydrogenase and α-ketoglutarate dehydrogenase (αKDH) complexes is a dynamically regulated process that is inhibited under hypoxia and in cancer cells to restrain mitochondrial respiration. Mechanistically, we found that the polymerase-δ interacting protein 2 (Poldip2), a nuclear-encoded mitochondrial protein of unknown function, controls the lipoylation of the pyruvate and α-KDH dihydrolipoamide acetyltransferase subunits by a mechanism that involves regulation of the caseinolytic peptidase (Clp)-protease complex and degradation of the lipoate-activating enzyme Ac-CoA synthetase medium-chain family member 1 (ACSM1)...
February 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
Cristina Nerin, Elena Canellas, Paula Vera, Estefanía Garcia-Calvo, José Luis Luque-Garcia, Carmen Cámara, Raquel Ausejo, Joaquín Miguel, Noelia Mendoza
Migration from a multilayer plastic material intended for food contact showed that 2,4,7,9-tetramethyl-5-decyne-4,7-diol mixture (surfynol), used as a surfactant in the adhesive employed to build the multilayer, was transferred to water and other food simulants in contact with the plastic. When these multilayer plastics were used for containing seminal doses for artificial insemination, it was found that fertility was seriously damaged in terms of motility, acrosome integrity, mitochondrial activity and penetration capacity in the cells, thus affecting male fertility...
January 30, 2018: Food and Chemical Toxicology
Alexandra M Huffman, Haotian Wu, Allyson Rosati, Tayyab Rahil, Cynthia K Sites, Brian W Whitcomb, J Richard Pilsner
BACKGROUND: Phthalates, a chemical class of plasticizers, are ubiquitous environmental contaminants that have been associated with oxidative stress. Mitochondria DNA copy number (mtDNAcn) and DNA deletions (mtDNAdel) are emerging biomarkers for cellular oxidative stress and environment exposures. OBJECTIVES: To examine associations of urinary phthalate metabolite and isoprostane concentrations on sperm mtDNAcn and mtDNAdel in male partners undergoing assisted reproductive technologies (ART)...
February 5, 2018: Environmental Research
Loredano Pollegioni, Luciano Piubelli, Gianluca Molla, Elena Rosini
pLG72 is a small, primate-specific protein of 153 amino acids. It is the product of the G72 gene, expressed in testis, spinal cord, and brain. The presence of G72 transcript and pLG72 has recurrently been called into question, however G72 mRNA and pLG72 protein levels were higher in blood and brain of patients with schizophrenia than in healthy controls. On the one hand, the SNP rs2391191 corresponding to the R30K substitution in pLG72 was genetically linked to schizophrenia, reduced thickness of the brain cortex in schizophrenia-affected individuals, and altered memory function...
2018: Frontiers in Molecular Biosciences
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