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Verena Zimorski, Cessa Rauch, Jaap J van Hellemond, Aloysius G M Tielens, William F Martin
In the presence of oxygen, Euglena gracilis mitochondria function much like mammalian mitochondria. Under anaerobiosis, E. gracilis mitochondria perform a malonyl-CoA independent synthesis of fatty acids leading to accumulation of wax esters, which serve as the sink for electrons stemming from glycolytic ATP synthesis and pyruvate oxidation. Some components (enzymes and cofactors) of Euglena's anaerobic energy metabolism are found among the anaerobic mitochondria of invertebrates, others are found among hydrogenosomes, the H2-producing anaerobic mitochondria of protists...
2017: Advances in Experimental Medicine and Biology
Gaurav Datta, Mohammad E Hossain, Mohd Asad, Sumit Rathore, Asif Mohmmed
The metabolic pathways associated with the mitochondrion and the apicoplast in Plasmodium, two parasite organelles of prokaryotic origin, are considered as suitable drug targets. In the present study, we have identified functional role of a novel OTU domain containing cysteine protease of Plasmodium falciparum (PfOTU). A C-terminal regulatable fluorescent affinity (RFA) tag on native protein was utilized for its localization and functional characterization. Detailed studies showed vesicular localization of PfOTU, and its association with the apicoplast...
April 18, 2017: Cellular Microbiology
Yafei Zhang, Jiazhong Wang, Hong Ji, Hongwei Lu, Le Lu, Jinlong Wang, Yiming Li
Hypoxia-reoxygenation (H/R) injury hepatocyte models were established to simulate the ischemia/reperfusion injury of transplanted organ. Through the study of the molecular mechanism of H/R on the F-actin damage of the liver cytomembrane, the mechanism of F-actin damage induced by ischemia and reperfusion was studied from the level of cell and molecule.The hypoxic environment of cells in vitro was simulated by chemical hypoxia agent CoCl2. Liver cells were detected by MTT, H/R group was subdivided into 3 subgroups: H/R 2, 4, and 6 h...
April 2017: Medicine (Baltimore)
Brian Panicucci, Ondřej Gahura, Alena Zíková
The mitochondrial (mt) FoF1-ATP synthase of the digenetic parasite, Trypanosoma brucei, generates ATP during the insect procyclic form (PF), but becomes a perpetual consumer of ATP in the mammalian bloodstream form (BF), which lacks a canonical respiratory chain. This unconventional dependence on FoF1-ATPase is required to maintain the essential mt membrane potential (Δψm). Normally, ATP hydrolysis by this rotary molecular motor is restricted to when eukaryotic cells experience sporadic hypoxic conditions, during which this compulsory function quickly depletes the cellular ATP pool...
April 17, 2017: PLoS Neglected Tropical Diseases
Han Shuwen, Yang Xi, Pan Yuefen
Colorectal cancer (CRC) was one of the most frequent cancers worldwide. Accurate risk and prognosis evaluation could obtain better quality of life and longer survival time for the patients. Current research hotspot was focus on the gene biomarker to evaluate the risk and prognosis. Mitochondrion contains its own DNA and regulates self-replicating so that it can be as a candidate biomarker for evaluating the risk and prognosis of colorectal cancer. But there were already huge controversies on this issue. The review was to summarize current viewpoints of the controversial issues and described our understanding from the four aspects including mtDNA copy number, mitochondrial displacement loop, mtDNA variation, and mtDNA microsatellite instability, wishing the summary of the mtDNA in colorectal cancer could provide a meaningful reference or a valuable direction in the future studies...
2017: Disease Markers
Laura J Bailey, Aidan J Doherty
PrimPol, (primase-polymerase), the most recently identified eukaryotic polymerase, has roles in both nuclear and mitochondrial DNA maintenance. PrimPol is capable of acting as a DNA polymerase, with the ability to extend primers and also bypass a variety of oxidative and photolesions. In addition, PrimPol also functions as a primase, catalysing the preferential formation of DNA primers in a zinc finger-dependent manner. Although PrimPol's catalytic activities have been uncovered in vitro, we still know little about how and why it is targeted to the mitochondrion and what its key roles are in the maintenance of this multicopy DNA molecule...
April 15, 2017: Biochemical Society Transactions
Zhen Zhao, Li Feng, Jiqin Wang, Deshan Cheng, Mei Liu, Meirong Ling, Weiping Xu, Keyu Sun
NPC-26 is novel mitochondrion-interfering compound. The current study tested its potential effect against colorectal cancer (CRC) cells. We demonstrated that NPC-26 induced potent anti-proliferative and cytotoxic activities against CRC cell lines (HCT-116, DLD-1 and HT-29). Activation of AMP-activated protein kinase (AMPK) signaling mediated NPC-26-induced CRC cell death. AMPKα1 shRNA knockdown or dominant negative mutation abolished NPC-26-induced AMPK activation and subsequent CRC cell death. NPC-26 disrupted mitochondrial function, causing mitochondrial permeability transition pore (mPTP) opening and reactive oxygen species (ROS) production...
March 14, 2017: Oncotarget
Ping Xu, Xingxia Liu, Xiwen Xiong, Wenbo Zhang, Xinhua Cai, Peiyong Qiu, Minghua Hao, Lijuan Wang, Dandan Lu, Xiuhua Zhang, Wancai Yang
Radioprotection is an important approach to reduce the side-effects of radiotherapy. The radioprotective effect of the flavonoids of Rosa roxburghii Tratt (FRT) has been confirmed, and the mechanism has been identified as theBcl-2/caspase-3/PARP-1 signaling pathway. In this study, we investigated the effects of FRT on the intercellular adhesion molecule (ICAM), and vascular cell adhesion protein (VCAM) in addition to apoptosis-related proteins such as Bax/Bcl-2, p-ERK/ERK, p-p53/p53, and p-p38/p38. In the present study, we focused on the effect of FRT on PARP-1/AIF...
April 11, 2017: Journal of Cellular Biochemistry
Jana Krech, Giang Tong, Sylvia Wowro, Christoph Walker, Lisa-Maria Rosenthal, Felix Berger, Katharina Rose Luise Schmitt
OBJECTIVE: Therapeutic hypothermia has been shown to attenuate myocardial cell death due to ischemia/reperfusion injury. However, cellular mechanisms of cooling remain to be elucidated. Especially during reperfusion, mitochondrial dysfunction contributes to cell death by releasing apoptosis inductors. The aim of the present study was to investigate the effects of moderate therapeutic hypothermia (33.5°C) on mitochondrial mediated apoptosis in ischemia/reperfusion-injured cardiomyocytes...
April 7, 2017: Mitochondrion
Yan-Yan Li, Yin Xiang, Song Zhang, Yan Wang, Jie Yang, Wei Liu, Feng-Tai Xue
The aim of this study is to examine the role of thioredoxin-2 (Trx2) in autophagy and apoptosis during myocardial ischemia-reperfusion (I/R) injury in vitro. We employed the oxygen-glucose deprivation and reperfusion (OGD/R) model of H9c2 cells and used lentiviral infection to overexpress Trx2. H9c2 cell viability and injury assays were conducted using a Cell Counting Kit-8 (CCK-8) and alactate dehydrogenase (LDH) kit. The effects of Trx2 on autophagy and apoptosis were measured by transmission electron microscopy (TEM), western blot, and flow cytometry...
2017: American Journal of Translational Research
Jingjing Deng, Kai Wang, Ming Wang, Ping Yu, Lanqun Mao
Zeolitic imidazole frameworks (ZIFs) are an emerging class of functional porous materials with promising biomedical applications such as molecular sensing and serving as nanocarriers for intracellular drug delivery. We present herein the first example of using nanoscale ZIFs (ZIF-90), self-assembled from Zn2+ and imidazole-2-carboxyaldehyde, to target subcellular mitochondrion, and to image the dynamic change of mitochondrial ATP in live cells. The encapsulation of fluorescent Rhodamine B (RhB) into ZIF-90 efficiently quenches the emission of RhB, while the competitive coordination between ATP and the metal node of ZIF-90 de-assembles ZIFs, resulting in the release of RhB for ATP sensing...
April 7, 2017: Journal of the American Chemical Society
Kylie Yang, Jacek L Kolanowski, Elizabeth J New
The balance of oxidants and antioxidants within the cell is crucial for maintaining health, and regulating physiological processes such as signalling. Consequently, imbalances between oxidants and antioxidants are now understood to lead to oxidative stress, a physiological feature that underlies many diseases. These processes have spurred the field of chemical biology to develop a plethora of sensors, both small-molecule and fluorescent protein-based, for the detection of specific oxidizing species and general redox balances within cells...
April 6, 2017: Interface Focus
Tingting Zhang, Wei Du, Andrew F Wilson, Satoshi H Namekawa, Paul R Andreassen, Amom Ruhikanta Meetei, Qishen Pang
Fancd2 is a component of the Fanconi anemia (FA) DNA repair pathway, which is frequently found defective in human cancers. The full repertoire of Fancd2 functions in normal development and tumorigenesis remains to be determined. Here we developed a Flag- and hemagglutinin-tagged Fancd2 knock-in mouse strain that allowed a high throughput mass spectrometry approach to search for Fancd2-binding proteins in different mouse organs. In addition to DNA repair partners, we observed that many Fancd2-interacting proteins are mitochondrion-specific...
April 5, 2017: Scientific Reports
Yanfen Cui, Yuanyuan Wang, Miao Liu, Li Qiu, Pan Xing, Xin Wang, Guoguang Ying, Binghui Li
Glucose is one of major nutrients and its catabolism provides energy and/or building bricks for cell proliferation. Glucose deficiency results in cell death. However, the underlying mechanism still remains elusive. By using our recently developed method to monitor real-time cellular apoptosis and necrosis, we show that glucose deprivation can directly elicit necrosis, which is promoted by mitochondrial impairment, depending on mitochondrial adenosine triphosphate (ATP) generation instead of ATP depletion. We demonstrate that glucose metabolism is the major source to produce protons...
March 25, 2017: Journal of Molecular Cell Biology
Chen Sun, Yu Cao, Pan Zhu, Bing Zhou
The potent anti-malarial drug artemisinins are additionally anti-tumorigenic and inhibitory to yeast growth. The action mechanism of artemisinins, however, is not well understood. Heme and mitochondrial membrane are both suggested to be involved in the action of artemisinins. Because heme is also synthesized in the mitochondrion, mitochondria appear to be a critical organelle for artemisinins' activities. In this study, we synthesized a mitochondria-targeting artemisinin derivative by conjugating triphenylphosphonium (TPP) to artelinic acid (ARTa)...
April 3, 2017: Scientific Reports
Alexander C Haindrich, Michala Boudová, Marie Vancová, Priscila Peña Diaz, Eva Horáková, Julius Lukeš
Sulfhydryl oxidase Erv1 is a ubiquitous and conserved protein of the mitochondrial intermembrane space that plays a role in the transport of small sulfur-containing proteins. In higher eukaryotes, Erv1 interacts with the mitochondrial import protein Mia40. However, Trypanosoma brucei lacks an obvious Mia40 homologue in its genome. Here we show by tandem affinity purification and mass spectrometry that in this excavate protist, Erv1 functions without a Mia40 homologue and most likely any other interaction partner...
March 31, 2017: Molecular and Biochemical Parasitology
Natália P Nogueira, Francis M S Saraiva, Matheus P Oliveira, Ana Paula M Mendonça, Job D F Inacio, Elmo E Almeida-Amaral, Rubem F Menna-Barreto, Gustavo A T Laranja, Eduardo J Lopes Torres, Marcus F Oliveira, Marcia C Paes
Trypanosoma cruzi is the causative agent of Chagas disease and has a single mitochondrion, an organelle responsible for ATP production and the main site for the formation of reactive oxygen species (ROS). T. cruzi is an obligate intracellular parasite with a complex life cycle that alternates between vertebrate and invertebrate hosts, therefore the development of survival strategies and morphogenetic adaptations to deal with the various environments is mandatory. Over the years our group has been studying the vector-parasite interactions using heme as a physiological oxidant molecule that triggered epimastigote proliferation however, the source of ROS induced by heme remained unknown...
March 29, 2017: Free Radical Biology & Medicine
Ralf J Braun, Ralf M Zerbes, Florian Steinberg, Denis Gris, Verónica I Dumit
Altered mitochondrial activities play an important role in many different human disorders, including cancer and neurodegeneration. At the Freiburg Institute of Advanced Studies (FRIAS) Junior Researcher Conference "One Mitochondrion, Many Diseases - Biological and Molecular Perspectives" (University of Freiburg, Freiburg, Germany), junior and experienced researches discussed common and distinct mechanisms of mitochondrial contributions to various human disorders.
November 4, 2016: Microbial Cell
Anna Karnkowska, Vladimír Hampl
Due to their involvement in the energy metabolism, mitochondria are essential for most eukaryotic cells. Microbial eukaryotes living in low oxygen environments possess reduced forms of mitochondria, namely mitochondrion-related organelles (MROs). These do not produce ATP by oxidative phosphorylation on their membranes and some do not produce ATP at all. Still, they are indispensable because of other essential functions such as iron-sulphur (Fe-S) cluster assembly. Recently, the first microbial eukaryote with neither mitochondrion nor MRO was characterized - Monocercomonoides sp...
September 30, 2016: Microbial Cell
Takayuki Fujiwara, Mio Ohnuma, Tsuneyoshi Kuroiwa, Ryudo Ohbayashi, Shunsuke Hirooka, Shin-Ya Miyagishima
The unicellular red alga Cyanidioschyzon merolae possesses a simple cellular architecture that consists of one mitochondrion, one chloroplast, one peroxisome, one Golgi apparatus, and several lysosomes. The nuclear genome content is also simple, with very little genetic redundancy (16.5 Mbp, 4,775 genes). In addition, molecular genetic tools such as gene targeting and inducible gene expression systems have been recently developed. These cytological features and genetic tractability have facilitated various omics analyses...
2017: Frontiers in Plant Science
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