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Mitochondria ETC AND Complex 1

David M Stucki, Céline Ruegsegger, Silvio Steiner, Julika Radecke, Michael P Murphy, Benoît Zuber, Smita Saxena
Spinocerebellar ataxia type 1 (SCA1), due to an unstable polyglutamine expansion within the ubiquitously expressed Ataxin-1 protein, leads to the premature degeneration of Purkinje cells (PCs), decreasing motor coordination and causing death within 10-15 years of diagnosis. Currently, there are no therapies available to slow down disease progression. As secondary cellular impairments contributing to SCA1 progression are poorly understood, here, we focused on identifying those processes by performing a PC specific proteome profiling of Sca1(154Q/2Q) mice at a symptomatic stage...
August 2016: Free Radical Biology & Medicine
Chad A Lerner, Pierrot Rutagarama, Tanveer Ahmad, Isaac K Sundar, Alison Elder, Irfan Rahman
Oxidants or nanoparticles have recently been identified as constituents of aerosols released from various styles of electronic cigarettes (E-cigs). Cells in the lung may be directly exposed to these constituents and harbor reactive properties capable of incurring acute cell injury. Our results show mitochondria are sensitive to both E-cig aerosols and aerosol containing copper nanoparticles when exposed to human lung fibroblasts (HFL-1) using an Air-Liquid Interface culture system, evident by elevated levels of mitochondrial ROS (mtROS)...
September 2, 2016: Biochemical and Biophysical Research Communications
Amelia Kate Pollard, Emma Louise Craig, Lisa Chakrabarti
Mitochondrial function, in particular complex 1 of the electron transport chain (ETC), has been shown to decrease during normal ageing and in neurodegenerative disease. However, there is some debate concerning which area of the brain has the greatest complex 1 activity. It is important to identify the pattern of activity in order to be able to gauge the effect of age or disease related changes. We determined complex 1 activity spectrophotometrically in the cortex, brainstem and cerebellum of middle aged mice (70-71 weeks), a cerebellar ataxic neurodegeneration model (pcd5J) and young wild type controls...
2016: PloS One
Song Cao, Yun Liu, Haiying Wang, Xiaowen Mao, Jincong Chen, Jiming Liu, Zhengyuan Xia, Lin Zhang, Xingkui Liu, Tian Yu
Ischemia postconditioning (IPo) is a promising strategy in reducing myocardial ischemia reperfusion (I/R) injury (MIRI), but its specific molecular mechanism is incompletely understood. Langendorff-perfused isolated rat hearts were subjected to global I/R and received IPo in the absence or presence of the mitochondrial ATP-sensitive potassium channel (mitoKATP) blocker 5-hydroxydecanoate (5-HD). Myocardial mitochondria were extracted and mitochondrial comparative proteomics was analyzed. IPo significantly reduces post-ischemic myocardial infarction and improved cardiac function in I/R rat hearts, while 5-HD basically cancelled IPo's myocardial protective effect...
2016: PeerJ
Fanchi Li, Kaizun Xu, Min Ni, Binbin Wang, Zhiya Gu, Weide Shen, Bing Li
Organophosphate pesticides are applied widely in the world for agricultural purposes, and their exposures often resulted in non-cocooning of Bombyx mori in China. Silkworm midgut is the major organ for digestion and nutrient absorption, importantly it is also a barrier against foreign substances and chemical pesticides. The purpose of this study was to determine the mechanism of oxidative injury in silkworm midgut with phoxim induction. The results showed that the transcription level of oxidative phosphorylation signaling pathway genes of midgut under phoxim stress...
January 2017: Environmental Toxicology
Qian Sun, Wei Zhong, Wenliang Zhang, Zhanxiang Zhou
Morphological and functional alterations of hepatic mitochondria have been documented in patients with alcoholic liver disease (ALD). Our recent study demonstrated that zinc level was decreased in whole liver and mitochondria by chronic alcohol feeding. The present study was undertaken to determine whether zinc deficiency mediates alcohol-induced mitochondrial electron transport chain (ETC) defect and whether defective ETC function may lead to generation of reactive oxygen species (ROS). Male Wistar rats were pair fed with the Lieber-DeCarli control or ethanol diet for 5 mo...
February 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Adeleye J Afolayan, Annie Eis, Maxwell Alexander, Teresa Michalkiewicz, Ru-Jeng Teng, Satyan Lakshminrusimha, Girija G Konduri
Impaired vasodilation in persistent pulmonary hypertension of the newborn (PPHN) is characterized by mitochondrial dysfunction. We investigated the hypothesis that a decreased endothelial nitric oxide synthase level leads to impaired mitochondrial biogenesis and function in a lamb model of PPHN induced by prenatal ductus arteriosus constriction. We ventilated PPHN lambs with 100% O2 alone or with inhaled nitric oxide (iNO). We treated pulmonary artery endothelial cells (PAECs) from normal and PPHN lambs with detaNONOate, an NO donor...
January 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Ru-Jeng Teng, Tzong-Jin Wu, Adeleye J Afolayan, Girija G Konduri
Nitration of both protein-bound and free tyrosine by reactive nitrogen species results in the formation of nitrotyrosine (NT). We previously reported that free NT impairs microtubule polymerization and uncouples endothelial nitric oxide synthase (eNOS) function in pulmonary artery endothelial cells (PAEC). Because microtubules modulate mitochondrial function, we hypothesized that increased NT levels during inflammation and oxidative stress will lead to mitochondrial dysfunction in PAEC. PAEC isolated from fetal lambs were exposed to varying concentrations of free NT...
January 1, 2016: American Journal of Physiology. Cell Physiology
Daniya Rakhmatullina, Anastasiya Ponomareva, Natalia Gazizova, Farida Minibayeva
Mitochondria are dynamic organelles, capable of fusion and fission as a part of cellular responses to various signals, such as the shifts in the redox status of a cell. The mitochondrial electron transport chain (ETC.) is involved in the generation of reactive oxygen species (ROS), with complexes I and III contributing the most to this process. Disruptions of ETC. can lead to increased ROS generation. Here, we demonstrate the appearance of giant mitochondria in wheat roots in response to simultaneous application of the respiratory inhibitors rotenone (complex I of mitochondrial ETC...
September 2016: Protoplasma
Prasenjit Prasad Saha, Shubhi Srivastava, Praveen Kumar S K, Devanjan Sinha, Patrick D'Silva
Biogenesis of the iron-sulfur (Fe-S) cluster is an indispensable process in living cells. In mammalian mitochondria, the initial step of the Fe-S cluster assembly process is assisted by the NFS1-ISD11 complex, which delivers sulfur to scaffold protein ISCU during Fe-S cluster synthesis. Although ISD11 is an essential protein, its cellular role in Fe-S cluster biogenesis is still not defined. Our study maps the important ISD11 amino acid residues belonging to putative helix 1 (Phe-40), helix 3 (Leu-63, Arg-68, Gln-69, Ile-72, Tyr-76), and C-terminal segment (Leu-81, Glu-84) are critical for in vivo Fe-S cluster biogenesis...
October 23, 2015: Journal of Biological Chemistry
Peng Zhang, Yong Lu, Dong Yu, Dadong Zhang, Wei Hu
BACKGROUND: Tumor necrosis factor receptor-associated protein 1 (TRAP1), an essential mitochondrial chaperone is induced in rat hearts following ischemia/reperfusion (I/R), but its role in myocardial I/R injury is unclear. The present study examined the function of TRAP1 in cardiomyocyte hypoxia/reoxygenation injury in vitro and myocardial I/R injury in vivo. METHODS: HL-1 cardiomyocytes transfected with TRAP1 or vector were subjected to simulated I/R (SI/R) in vitro...
2015: Cellular Physiology and Biochemistry
D L Kolesnik, O N Pyaskovskaya, I V Boychuk, O I Dasyukevich, O R Melnikov, A S Tarasov, G I Solyanik
UNLABELLED: A hallmark of malignancy is excessive tumor glycolysis, even in the presence of oxygen, which causes lactacidosis in the tumor microenvironment and favors tumor cell proliferation and survival. For this reason antimetabolic agents which target tumor cell metabolism are being researched extensively as promising anticancer drugs. AIM: To study the effect of lactacidosis on survival of Lewis lung carcinoma (LLC) cells at the conditions of nutritional substrate deficiency in vitro and evaluate antitumor and antimetastatic activity against LLC/R9 in vivo...
June 2015: Experimental Oncology
Omar Ortiz-Avila, Marco Alonso Gallegos-Corona, Luis Alberto Sánchez-Briones, Elizabeth Calderón-Cortés, Rocío Montoya-Pérez, Alain R Rodriguez-Orozco, Jesús Campos-García, Alfredo Saavedra-Molina, Ricardo Mejía-Zepeda, Christian Cortés-Rojo
Electron transport chain (ETC) dysfunction, excessive ROS generation and lipid peroxidation are hallmarks of mitochondrial injury in the diabetic liver, with these alterations also playing a role in the development of non-alcoholic fatty liver disease (NAFLD). Enhanced mitochondrial sensitivity to lipid peroxidation during diabetes has been also associated to augmented content of C22:6 in membrane phospholipids. Thus, we aimed to test whether avocado oil, a rich source of C18:1 and antioxidants, attenuates the deleterious effects of diabetes on oxidative status of liver mitochondria by decreasing unsaturation of acyl chains of membrane lipids and/or by improving ETC functionality and decreasing ROS generation...
August 2015: Journal of Bioenergetics and Biomembranes
Hye Jin Hwang, Scott G Lynn, Ajith Vengellur, Yogesh Saini, Elizabeth A Grier, Shelagh M Ferguson-Miller, John J LaPres
Hypoxia inducible factor-1 (HIF1) is a stress-responsive nuclear transcription factor that is activated with a decrease in oxygen availability. HIF1 regulates the expression of genes involved in a cell's adaptation to hypoxic stress, including those with mitochondrial specific function. To gain a more comprehensive understanding of the role of HIF1 in mitochondrial homeostasis, we studied the link between hypoxia, HIF1 transactivation, and electron transport chain (ETC) function. We established immortalized mouse embryonic fibroblasts (MEFs) for HIF1α wild-type (WT) and null cells and tested whether HIF1α regulates mitochondrial respiration by modulating gene expressions of nuclear-encoded ETC components...
June 23, 2015: Biochemistry
J Brian Morgan, Yang Liu, Veena Coothankandaswamy, Fakhri Mahdi, Mika B Jekabsons, William H Gerwick, Frederick A Valeriote, Yu-Dong Zhou, Dale G Nagle
The biologically active lipopeptide kalkitoxin was previously isolated from the marine cyanobacterium Moorea producens (Lyngbya majuscula). Kalkitoxin exhibited N-methyl-D-aspartate (NMDA)-mediated neurotoxicity and acted as an inhibitory ligand for voltage-sensitive sodium channels in cultured rat cerebellar granule neurons. Subsequent studies revealed that kalkitoxin generated a delayed form of colon tumor cell cytotoxicity in 7-day clonogenic cell survival assays. Cell line- and exposure time-dependent cytostatic/cytotoxic effects were previously observed with mitochondria-targeted inhibitors of hypoxia-inducible factor-1 (HIF-1)...
March 2015: Marine Drugs
Clare Edwards, John Canfield, Neil Copes, Andres Brito, Muhammad Rehan, David Lipps, Jessica Brunquell, Sandy D Westerheide, Patrick C Bradshaw
BACKGROUND: Little is known about the role of amino acids in cellular signaling pathways, especially as it pertains to pathways that regulate the rate of aging. However, it has been shown that methionine or tryptophan restriction extends lifespan in higher eukaryotes and increased proline or tryptophan levels increase longevity in C. elegans. In addition, leucine strongly activates the TOR signaling pathway, which when inhibited increases lifespan. RESULTS: Therefore each of the 20 proteogenic amino acids was individually supplemented to C...
2015: BMC Genetics
Felix Distelmaier, Federica Valsecchi, Dania C Liemburg-Apers, Magdalena Lebiedzinska, Richard J Rodenburg, Sandra Heil, Jaap Keijer, Jack Fransen, Hiromi Imamura, Katharina Danhauser, Annette Seibt, Benoit Viollet, Frank N Gellerich, Jan A M Smeitink, Mariusz R Wieckowski, Peter H G M Willems, Werner J H Koopman
Dysfunction of complex I (CI) of the mitochondrial electron transport chain (ETC) features prominently in human pathology. Cell models of ETC dysfunction display adaptive survival responses that still are poorly understood but of relevance for therapy development. Here we comprehensively examined how primary human skin fibroblasts adapt to chronic CI inhibition. CI inhibition triggered transient and sustained changes in metabolism, redox homeostasis and mitochondrial (ultra)structure but no cell senescence/death...
March 2015: Biochimica et Biophysica Acta
Luis Valmor Portela, Jussania Gnoatto, Andressa Wigner Brochier, Clarissa Branco Haas, Adriano Martimbianco de Assis, Afonso Kopczynski de Carvalho, Gisele Hansel, Eduardo Rigon Zimmer, Jean Pierre Oses, Alexandre Pastoris Muller
Metformin (Met), which is an insulin-sensitizer, decreases insulin resistance and fasting insulin levels. The precise molecular target of Met is unknown; however, several reports have shown an inhibitory effect on mitochondrial complex I of the electron transport chain (ETC), which is a related site for reactive oxygen species production. In addition to peripheral effects, Met is capable of crossing the blood-brain barrier, thus regulating the central mechanism involved in appetite control. The present study explores the effects of intracerebroventricular (i...
March 2015: Neurochemical Research
Dharendra Thapa, Cody E Nichols, Sara E Lewis, Danielle L Shepherd, Rajaganapathi Jagannathan, Tara L Croston, Kevin J Tveter, Anthony A Holden, Walter A Baseler, John M Hollander
Mitofilin, also known as heart muscle protein, is an inner mitochondrial membrane structural protein that plays a central role in maintaining cristae morphology and structure. It is a critical component of the mitochondrial contact site and cristae organizing system (MICOS) complex which is important for mitochondrial architecture and cristae morphology. Our laboratory has previously reported alterations in mitochondrial morphology and proteomic make-up during type 1 diabetes mellitus, with mitofilin being significantly down-regulated in interfibrillar mitochondria (IFM)...
February 2015: Journal of Molecular and Cellular Cardiology
Gisela Beutner, Roman A Eliseev, George A Porter
Mitochondria provide energy in form of ATP in eukaryotic cells. However, it is not known when, during embryonic cardiac development, mitochondria become able to fulfill this function. To assess this, we measured mitochondrial oxygen consumption and the activity of the complexes (Cx) 1 and 2 of the electron transport chain (ETC) and used immunoprecipitation to follow the generation of mitochondrial supercomplexes. We show that in the heart of mouse embryos at embryonic day (E) 9.5, mitochondrial ETC activity and oxidative phosphorylation (OXPHOS) are not coupled, even though the complexes are present...
2014: PloS One
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