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Mitochondria ETC AND Complex 1

Kuo Du, Anup Ramachandran, Mitchell R McGill, Abdellah Mansouri, Tarik Asselah, Anwar Farhood, Benjamin L Woolbright, Wen-Xing Ding, Hartmut Jaeschke
Mitochondrial biogenesis (MB) is an adaptive response to maintain metabolic homeostasis after mitochondrial dysfunction. Induction of MB during APAP hepatotoxicity has not been studied. To investigate this, mice were treated with toxic doses of APAP and euthanized between 0 and 96 h. At early time points, APAP caused both mitochondrial dysfunction and reduction of mitochondrial mass, indicated by reduced activity of electron transport chain (ETC) complexes I and IV and depletion of mitochondrial DNA (mtDNA), respectively...
October 2017: Food and Chemical Toxicology
Sehwan Jang, Sabzali Javadov
Although mitochondrial Ca(2+) overload and ROS production play a critical role in mitochondria-mediated cell death, a cause-effect relationship between them remains elusive. This study elucidated the crosstalk between mitochondrial swelling, ROS production, and electron transfer chain (ETC) supercomplexes in rat heart mitochondria in response to Ca(2+) and tert-butyl hydroperoxide (TBH), a lipid-soluble organic peroxide. Results showed that ROS production induced by TBH was significantly increased in the presence of Ca(2+) in a dose-dependent manner...
September 15, 2017: Archives of Biochemistry and Biophysics
Hsin-Wen Chang, Steve Pisano, Amaresh Chaturbedi, Jennifer Chen, Sarah Gordon, Aiswarya Baruah, Siu Sylvia Lee
A decline in mitochondrial electron transport chain (ETC) function has long been implicated in aging and various diseases. Recently, moderate mitochondrial ETC dysfunction has been found to prolong lifespan in diverse organisms, suggesting a conserved and complex role of mitochondria in longevity determination. Several nuclear transcription factors have been demonstrated to mediate the lifespan extension effect associated with partial impairment of the ETC, suggesting that compensatory transcriptional response to be crucial...
August 2017: Aging Cell
Shih-Chieh Chiang, Martin Meagher, Nick Kassouf, Majid Hafezparast, Peter J McKinnon, Rachel Haywood, Sherif F El-Khamisy
Breakage of one strand of DNA is the most common form of DNA damage. Most damaged DNA termini require end-processing in preparation for ligation. The importance of this step is highlighted by the association of defects in the 3'-end processing enzyme tyrosyl DNA phosphodiesterase 1 (TDP1) and neurodegeneration and by the cytotoxic induction of protein-linked DNA breaks (PDBs) and oxidized nucleic acid intermediates during chemotherapy and radiotherapy. Although much is known about the repair of PDBs in the nucleus, little is known about this process in the mitochondria...
April 2017: Science Advances
Kyeong-Ah Jung, Sujin Lee, Mi-Kyoung Kwak
AIMS: The nuclear factor (erythroid-derived 2)-like 2 (NFE2L2; NFE2L2/NRF2) pathway contributes to the environmental resistance of cancers by enhancing the antioxidant capacity. Here, we explored the potential connection between NFE2L2/NRF2 and mitochondrial function in cancers. RESULTS: Global miRNA expression analysis of HT29 and HCT116 human colon cancer cells identified that NFE2L2/NRF2 silencing upregulated miR-181c through nuclear factor-κB signaling, and this increase was associated with the reduction in mitochondria-encoded cytochrome c oxidase subunit-1 (MT-CO1), a catalytic core subunit of the complex IV of the electron transport chain (ETC)...
April 6, 2017: Antioxidants & Redox Signaling
Yang Xue, Qingqing Chen, Jiao Sun
Hydroxyapatite nanoparticles (HAP-NPs) have been extensively developed as drug carriers, bone implants, coating materials, etc. in the human body. However, research focusing on the potential side effects of HAP-NPs on the mitochondria-associated energy metabolism in liver cells is lacking. In this study, HAP-NPs with a long diameter of 80 nm and a short diameter of 20 nm were evaluated for their ability to induce mitochondrial energy metabolism dysfunction in vitro and in vivo. In the in vitro system, the buffalo rat hepatocyte (BRL) cell line was directly exposed to the HAP-NPs...
March 6, 2017: Journal of Applied Toxicology: JAT
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
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