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Jenna L Gollihue, Samir P Patel, Alexander G Rabchevsky
Mitochondria are essential cellular organelles critical for generating adenosine triphosphate for cellular homeostasis, as well as various mechanisms that can lead to both necrosis and apoptosis. The field of "mitochondrial medicine" is emerging in which injury/disease states are targeted therapeutically at the level of the mitochondrion, including specific antioxidants, bioenergetic substrate additions, and membrane uncoupling agents. Consequently, novel mitochondrial transplantation strategies represent a potentially multifactorial therapy leading to increased adenosine triphosphate production, decreased oxidative stress, mitochondrial DNA replacement, improved bioenergetics and tissue sparing...
February 2018: Neural Regeneration Research
Jenq-Lin Yang, Sujira Mukda, Shang-Der Chen
Stroke is the leading cause of adult disability and mortality in most developing and developed countries. The current best practices for patients with acute ischemic stroke include intravenous tissue plasminogen activator and endovascular thrombectomy for large-vessel occlusion to improve clinical outcomes. However, only a limited portion of patients receive thrombolytic therapy or endovascular treatment because the therapeutic time window after ischemic stroke is narrow. To address the current shortage of stroke management approaches, it is critical to identify new potential therapeutic targets...
March 9, 2018: Redox Biology
Lilian Cristina Pereira, Murilo Pazin, Mariana Furio Franco-Bernardes, Airton da Cunha Martins, Gustavo Rafael Mazzaron Barcelos, Márcio Cesar Pereira, João Paulo Mesquita, Jairo Lisboa Rodrigues, Fernando Barbosa, Daniel Junqueira Dorta
Nanotechnology is a growing branch of science that deals with the development of structural features bearing at least one dimension in the nano range. More specifically, nanomaterials are defined as objects with dimensions that range from 1 to 100 nm, which give rise to interesting properties. In particular, silver and titanium nanoparticles (AgNPs and TiNPs, respectively) are known for their biological and biomedical properties and are often used in consumer products such as cosmetics, food additives, kitchen utensils, and toys...
May 2018: Journal of Trace Elements in Medicine and Biology
Godwin U Ebiloma, Teresa Díaz Ayuga, Emmanuel O Balogun, Lucía Abad Gil, Anne Donachie, Marcel Kaiser, Tomás Herraiz, Daniel K Inaoka, Tomoo Shiba, Shigeharu Harada, Kiyoshi Kita, Harry P de Koning, Christophe Dardonville
African trypanosomiasis is a neglected parasitic disease that is still of great public health relevance, and a severe impediment to agriculture in endemic areas. The pathogens possess certain unique metabolic features that can be exploited for the development of new drugs. Notably, they rely on an essential, mitochondrially-localized enzyme, Trypanosome Alternative Oxidase (TAO) for their energy metabolism, which is absent in the mammalian hosts and therefore an attractive target for the design of safe drugs...
February 26, 2018: European Journal of Medicinal Chemistry
Yannan Zhao, Lilan Luo, Jiesi Xu, Peiyong Xin, Hongyan Guo, Jian Wu, Lin Bai, Guodong Wang, Jinfang Chu, Jianru Zuo, Hong Yu, Xun Huang, Jiayang Li
Programmed cell death (PCD) is a fundamental biological process. Deficiency in MOSAIC DEATH 1 (MOD1), a plastid-localized enoyl-ACP reductase, leads to the accumulation of reactive oxygen species (ROS) and PCD, which can be suppressed by mitochondrial complex I mutations, indicating a signal from chloroplasts to mitochondria. However, this signal remains to be elucidated. In this study, through cloning and analyzing a series of mod1 suppressors, we reveal a comprehensive organelle communication pathway that regulates the generation of mitochondrial ROS and triggers PCD...
March 14, 2018: Cell Research
Li Wang, Jing-Jing Li, Li-Yu Guo, Peipei Li, Zhiqiang Zhao, Haisheng Zhou, Li-Jun Di
Glucose and Glutamine are two essential ingredients for cell growth. However, it remains open for investigation whether there is a general mechanism that coordinates the consumption of glucose and glutamine in cancer cells. Glutamine is mainly metabolized through the glutaminolysis pathway and our previous report indicated that CtBP increases GDH activity and promotes glutaminolysis through repressing the expression of SIRT4, a well-known mitochondrion-located factor that inhibits glutaminolysis pathway. CtBP is known to be a sensor of intracellular metabolic status; we thus hypothesized that a consensus CtBP-SIRT4-GDH axis may mediate the crosstalk between glycolysis and glutaminolysis...
March 13, 2018: Oncogenesis
Dinesh Kumar Verma, Sonam Gupta, Joyshree Biswas, Neeraj Joshi, K Sivarama Raju, Mu Wahajuddin, Sarika Singh
Piracetam, a nootropic drug, has been clinically used for decades; however, its mechanism of action still remains enigmatic. The present study was undertaken to evaluate the role of mitochondrion-specific factors of caspase-independent pathway like apoptotic-inducing factor (AIF) and endonuclease-G (endo-G) in piracetam-induced neuroprotection. N2A cells treated with lipopolysaccharide (LPS) exhibited significant cytotoxicity, impaired mitochondrial activity, and reactive oxygen species generation which was significantly attenuated with piracetam co-treatment...
March 12, 2018: Neurotoxicity Research
Chunyan Hao, Hubin Duan, Hao Li, Huan Wang, Yueting Liu, Yimin Fan, Ce Zhang
Mammalian mitochondrial ribosomal proteins are functionally involved in protein synthesis in mitochondrion. Recently numerous studies have illuminated the role of mitochondrion in cancer development. However, the precise function of MRPL42 remains unclear. Here in this study, we identified MRPL42 as a novel oncogene in glioma. By analyzing the Cancer Genome Atlas (TCGA) database, we firstly found that MRPL42 was significantly up-regulated in glioma tissues compared with normal tissues. Functionally, we silenced MRPL42 in glioma cells and revealed that MRPL42 knockdown largely blunted the proliferation of U251 and A172 cells...
March 12, 2018: Bioscience Reports
Helen Hernández, Alejandra Parra, Nicolas Tobar, Jessica Molina, Violeta Kallens, Miltha Hidalgo, Diego Varela, Jorge Martínez, Omar Porras
Aerobic metabolism brings inexorably the production of reactive oxygen species (ROS), which are counterbalanced by intrinsic antioxidant defenses avoiding deleterious intracellular effects. Redox balance is the resultant of metabolic functioning under environmental inputs (i.e. diet, pollution) and the activity of intrinsic antioxidant machinery. Monitoring of intracellular hydrogen peroxide has been successfully achieved by redox biosensor advent; however, to track the intrinsic disulfide bond reduction capacity represents a fundamental piece to understand better how redox homeostasis is maintained in living cells...
March 2, 2018: Redox Biology
Ke Chen, Yuxuan Wang, Jie Sun
The Alu-element plays important roles in mediating alternative splicing, RNA editing and translation regulation. However, the distribution and function of the Alu-element are never analysed at the transcriptome level. This study presents a statistical analysis of the Alu-element on human transcriptome. We found that mRNAs and lncRNAs share the same sequence form for the Alu-element. The Alu-element covers 5.8% of the coding transcripts and 17.1% of the coding genes for mRNAs, and covers 9.3% of the transcripts and 13...
March 7, 2018: Biochemical and Biophysical Research Communications
Qi-Lin Zhang, Xing-Zhuo Yang, Li Zhang, Run-Qiu Feng, Qian-Hua Zhu, Jun-Yuan Chen, Ming-Long Yuan
Given mitochondrion is the 'energy and oxygen usage factories', adaptive signatures of mitochondrial genes have been extensively investigated in vertebrates from different altitudes, but few studies focus on insects. Here, we sequenced the complete mitochondrial genome (mitogenome) of Dolycoris. baccarum living in the Tibetan Plateau (DBHC, ∼3200 m above sea level (asl)) and conducted a detailed comparative analysis with another D. baccarum mitogenome (DBQY) from relatively low altitude (∼1300 m asl)...
March 9, 2018: Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis
Rui Zeng, Erin Smith, Antoni Barrientos
Mitoribosomes are specialized for the synthesis of hydrophobic membrane proteins encoded by mtDNA, all essential for oxidative phosphorylation. Despite their linkage to human mitochondrial diseases and the recent cryoelectron microscopy reconstruction of yeast and mammalian mitoribosomes, how they are assembled remains obscure. Here, we dissected the yeast mitoribosome large subunit (mtLSU) assembly process by systematic genomic deletion of 44 mtLSU proteins (MRPs). Analysis of the strain collection unveiled 37 proteins essential for functional mtLSU assembly, three of which are critical for mtLSU 21S rRNA stability...
March 6, 2018: Cell Metabolism
Asha Lekshmi, Shankara Narayanan Varadarajan, Santhik Subhasingh Lupitha, Mydhily Nair, Aneesh Chandrasekharan, T R Santhoshkumar
Recent cell biology studies reveal that a cell can die through multiple pathways via distinct signaling mechanisms. Among these, apoptosis and necrosis are two distinct cell death pathways, and their detection and discrimination is vital in the drug discovery process and in understanding diverse biological processes. Although sensitive assays for apoptosis and necrosis are available, it is extremely difficult to adapt any of these methods to discriminate apoptosis-inducing stimuli from necrosis-inducing stimuli because of the acquisition of secondary necrosis by apoptotic cells when they are not phagocytosed...
February 21, 2018: Current Protocols in Toxicology
Daria Tashyreva, Galina Prokopchuk, Jan Votýpka, Akinori Yabuki, Aleš Horák, Julius Lukeš
Diplonemids represent a hyperdiverse and abundant yet poorly studied group of marine protists. Here we describe two new members of the genus Diplonema (Diplonemea, Euglenozoa), Diplonema japonicum sp. nov. and Diplonema aggregatum sp. nov., based on life cycle, morphology, and 18S rRNA gene sequences. Along with euglenozoan apomorphies, they contain several unique features. Their life cycle is complex, consisting of a trophic stage that is, following the depletion of nutrients, transformed into a sessile stage and subsequently into a swimming stage...
March 6, 2018: MBio
Ari Dwi Nugraheni, Chunguang Ren, Yorifumi Matsumoto, Satoshi Nagao, Masaru Yamanaka, Shun Hirota
The Met80-heme iron bond of cytochrome c (cyt c) is cleaved by the interaction of cyt c with cardiolipin (CL) in membranes. The Met80 dissociation enhances the peroxidase activity of cyt c and triggers cyt c release from mitochondrion to the cytosol at the early stage of apoptosis. This paper demonstrates the selective oxidation of Met80 for the reaction of ferric cyt c with a peroxide, meta-chloroperbenzoic acid (mCPBA), in the presence of CL-containing liposomes by formation of a ferryl species (Compound I)...
February 24, 2018: Journal of Inorganic Biochemistry
Dongjie Liu, Mingyang Liu, Wenjing Wang, Lijun Pang, Zhenchang Wang, Chunwang Yuan, Kai Liu
Full-length apoptosis-inducing factor mitochondrion-associated 1 (AIFM1) (∼67 kDa) induces apoptosis in a caspase-independent manner when it is cleaved at its N-terminus to produce truncated AIFM1 (∼57 kDa). Here, we produced recombinant adenovirus AIFM1 (rAd-AIFM1) encoding full-length AIFM1 to detect whether full-length AIFM1 suppresses cell growth and induces apoptosis of hepatoma cell lines (HepG2 and Hep3B). Hepatocellular carcinoma (HCC) is one of the most difficult cancers to treat worldwide...
February 28, 2018: Biochemical and Biophysical Research Communications
Setsuko Komatsu, Akiko Hashiguchi
Soybean, which is rich in protein and oil, is cultivated in several climatic zones; however, its growth is markedly decreased by flooding. Proteomics is a useful tool for understanding the flooding-response mechanism in soybean. Subcellular proteomics has the potential to elucidate localized cellular responses and investigate communications among subcellular components during plant growth and during stress. Under flooding, proteins related to signaling, stress and the antioxidative system are increased in the plasma membrane; scavenging enzymes for reactive-oxygen species are suppressed in the cell wall; protein translation is suppressed through inhibition of proteins related to preribosome biogenesis and mRNA processing in the nucleus; levels of proteins involved in the electron transport chain are reduced in the mitochondrion; and levels of proteins related to protein folding are decreased in the endoplasmic reticulum...
February 27, 2018: Proteomes
Dustin C Ernst, Diana M Downs
A variety of metabolic deficiencies and human diseases arise from the disruption of mitochondrial enzymes and/or loss of mitochondrial DNA. Mounting evidence shows that eukaryotes have conserved enzymes that prevent the accumulation of reactive metabolites that cause stress inside the mitochondrion. 2-Aminoacrylate is a reactive enamine generated by pyridoxal 5'-phosphate-dependent α,β-eliminases as an obligatory intermediate in the breakdown of serine. In prokaryotes, members of the broadly conserved RidA family (PF14588) prevent metabolic stress by deaminating 2-aminoacrylate to pyruvate...
February 27, 2018: MBio
Siqi Tian, Akinori Ohta, Hiroyuki Horiuchi, Ryouichi Fukuda
Sterols are present in eukaryotic membranes and significantly affect membrane fluidity, permeability, and microdomain formation. They are synthesized in the endoplasmic reticulum (ER) and transported to other organelles and the plasma membrane. Sterols play important roles in the biogenesis and maintenance of mitochondrial membranes. However, the mechanisms underlying ER-to-mitochondrion sterol transport remain to be identified. Here, using purified yeast membrane fractions enriched in ER and mitochondria, we show that the oxysterol-binding protein homologs encoded by the OSH genes in the yeast Saccharomyces cerevisiae mediate sterol transport from the ER to mitochondria...
February 27, 2018: Journal of Biological Chemistry
Maria Tsoli, Jie Liu, Laura Franshaw, Han Shen, Cecilia Cheng, MoonSun Jung, Swapna Joshi, Anahid Ehteda, Aaminah Khan, Angel Montero-Carcabosso, Pierre J Dilda, Philip Hogg, David S Ziegler
Diffuse Intrinsic Pontine Gliomas (DIPG) are the most devastating of all pediatric brain tumors. They mostly affect young children and, as there are no effective treatments, almost all patients with DIPG will die of their tumor within 12 months of diagnosis. A key feature of this devastating tumor is its intrinsic resistance to all clinically available therapies. It has been shown that glioma development is associated with metabolic reprogramming, redox state disruption and resistance to apoptotic pathways...
January 26, 2018: Oncotarget
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