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Rebecca Hanna, Jonathan M Crowther, Pallav A Bulsara, Xuying Wang, David J Moore, Mark A Birch-Machin
Intrinsic and extrinsic factors that induce cellular oxidative stress damage tissue integrity and promote ageing, resulting in accumulative strand breaks to the mitochondrial DNA (mtDNA) genome. Limited repair mechanisms and close proximity to superoxide generation make mtDNA a prominent biomarker of oxidative damage. Using human DNA we describe an optimised long-range qPCR methodology that sensitively detects mtDNA strand breaks relative to a suite of short mitochondrial and nuclear DNA housekeeping amplicons, which control for any variation in mtDNA copy number...
May 3, 2018: Mitochondrion
Vitaly D Samuilov, Dmitry B Kiselevsky, Alexander V Oleskin
This work focuses on the effect of mitochondria-targeted quinones (SkQs) on plants. SkQs with antioxidant properties are accumulated in the mitochondria of pea cells and suppress the generation of reactive oxygen species. At nanomolar concentrations, SkQs prevented the death of pea leaf epidermal or guard cells caused by chitosan, bacterial lipopolysaccharide or KCN. The protective effect of SkQs was removed by a protonophoric uncoupler. SkQs at micromolar concentrations inhibited the O2 evolution by illuminated chloroplasts and stimulated the respiration of mitochondria...
April 30, 2018: Mitochondrion
Deepa R Avisetti, Niharika Amireddy, Shasi V Kalivendi
Amongst various therapeutic properties of the natural product embelin, its anti-cancer effects are being extensively studied. We observed that, embelin induced apoptosis in A549 cells lacking functional mitochondria (ρ0 cells) indicating that its mitochondrial effects are not primarily responsible for its anti-cancer activity. However, p38 mediated activation of p53 was found to play a pivotal role in governing the apoptotic activity of embelin due to the following observations: a time-dependent activation of p53 and apoptosis by embelin; selective inhibition of p38 inhibited embelin-induced p53 levels...
April 28, 2018: Mitochondrion
Daniel Jablonski, Václav Gvoždík, Lukáš Choleva, David Jandzik, Jiří Moravec, Zdeněk Mačát, Milan Veselý
The maternal origin of isolated populations of the common wall lizard (Podracis muralis) in the Czech Republic, representing the north-eastern range border of the species, was addressed. We compared mitochondrial DNA sequences of the cytochrome b gene of samples from these populations with those from within the continuous range in Slovakia, the northern Balkan region, and those available from previous studies. We recorded five main haplogroups in the studied region, with all available Central European samples belonging to the same haplogroup...
April 22, 2018: Mitochondrion
Talisa K Silzer, Nicole R Phillips
Type 2 diabetes is a significant risk factor for developing Alzheimer's disease later in life, and particular populations have a disproportionate risk because of the high prevalence of type 2 diabetes. There are many overlapping pathologies, and teasing out the primary root cause, if one indeed exists, is very difficult. Here, we review (1) the key facets of mitochondrial biology that are relevant to the two conditions, and (2) the role that mitochondrial dysfunction plays in the shared pathophysiology. We posit that mitochondrial dysfunction lies at the root of the affected processes rather than alongside them as a co-pathology...
April 17, 2018: Mitochondrion
Sunil Kumar Saini, Ponnusamy Kalaiarasan, Rajnish Kumar Singh, Siddharth Manvati, R N K Bamezai
The present study on the basis of a detailed bioinformatics analysis proposed a potential role of a miRNA, hsa-miR-19b-2-5p, in regulating the mitochondrial biogenesis. The miRNA has shown to be involved in important biological processes of cellular metabolic, cellular macromolecule biosynthetic processes and gene expression pathways. The miRNA, hsa-miR-19b-2-5p, was predicted to regulate the molecular function of nucleic acid, organic/heterocyclic compound, nucleic acid binding transcription factor activity...
April 17, 2018: Mitochondrion
Srinivasu Karri, Swati Singh, Arun Kumar Paripati, Adinarayana Marada, Thanuja Krishnamoorthy, Lalitha Guruprasad, Dorairajan Balasubramanian, Naresh Babu V Sepuri
Perturbations in mitochondrial redox levels oxidize nucleotide exchanger Mge1, compromising its ability to bind to the Hsp70, while the Mxr2 enzyme reduces the oxidized Mge1. However, the effects of persistent oxidative stress on Mge1 structure and function are not known. In this study, we show that oxidation-induced selective and local structural adaptations cause the detachment of Mge1 from Hsp70. Notably, persistent oxidative stress causes monomeric Mge1 to aggregate and to generate amyloid-type particles...
April 9, 2018: Mitochondrion
Bruno Cavadas, Joana B Pereira, Marcelo Correia, Verónica Fernandes, Catarina Eloy, Manuel Sobrinho-Simões, Paula Soares, David C Samuels, Valdemar Máximo, Luisa Pereira
We conducted the first systematic omics study of the oncocytic phenotype in 488 papillary thyroid carcinomas (PTC) from The Cancer Genome Atlas. Oncocytic phenotype is secondary to PTC, being unrelated to several pathologic scores. The nuclear genome had low impact on this phenotype (except in specific copy number variation), which was mostly driven by the significant accumulation of mitochondrial DNA non-synonymous and frameshift mutations at high heteroplasmy levels. Energy and mitochondrial-related pathways were significantly enriched in oncocytic tumors that also displayed increased levels of expression for genes involved in autophagy and fusion of mitochondria...
April 6, 2018: Mitochondrion
Bernard W M Wone, Won C Yim, Heidi Schutz, Thomas H Meek, Theodore Garland
Mitochondrial haplotypes have been associated with human and rodent phenotypes, including nonshivering thermogenesis capacity, learning capability, and disease risk. Although the mammalian mitochondrial D-loop is highly polymorphic, D-loops in laboratory mice are identical, and variation occurs elsewhere mainly between nucleotides 9820 and 9830. Part of this region codes for the tRNAArg gene and is associated with mitochondrial densities and number of mtDNA copies. We hypothesized that the capacity for high levels of voluntary wheel-running behavior would be associated with mitochondrial haplotype...
April 4, 2018: Mitochondrion
Giovanna Ramirez-Barbieri, Kamila Moskowitzova, Borami Shin, David Blitzer, Arzoo Orfany, Alvise Guariento, Khadija Iken, Ingeborg Friehs, David Zurakowski, Pedro J Del Nido, James D McCully
Previously, we have demonstrated that the transplantation of autologous mitochondria is cardioprotective. No immune or autoimmune response was detectable following the single injection of autologous mitochondria. To expand the therapeutic potential and safety of mitochondrial transplantation, we now investigate the immune response to single and serial injections of syngeneic and allogeneic mitochondria delivered by intraperitoneal injection. Our results demonstrate that there is no direct or indirect, acute or chronic alloreactivity, allorecognition or damage-associated molecular pattern molecules (DAMPs) reaction to single or serial injections of either syngeneic or allogeneic mitochondria...
March 26, 2018: Mitochondrion
Paula M Miotto, Graham P Holloway
Acute exercise rapidly induces mitochondrial gene expression, however, the intracellular events regulating this process remain incompletely understood. The purpose of this study was to determine whether reductions in mitochondrial ADP sensitivity during exercise have a biological role in regulating mitochondrial-derived reactive oxygen species (ROS) production and the induction of mitochondrial biogenesis. Mitochondrial creatine kinase wildtype (WT) and knockout (KO) mice have divergent responses in ADP sensitivity during exercise, and we therefore used these mice to determine the relationship between mitochondrial ADP sensitivity, ROS production, and mitochondrial adaptations to exercise...
March 24, 2018: Mitochondrion
Sayaka Kazami, Shingo Nishiyama, Yuji Kimura, Hiroyasu Itoh, Hideo Tsukada
BCPP compounds have been developed as PET imaging probes for neurodegenerative diseases in the living brain. 18 F-BCPP-EF identifies damaged neuronal areas based on the lack of MC-I; however, its underlying mechanisms of action and specificity for MC-I remain unclear. We herein report the effects of BCPP-BF, -EF, -EM on MC-I in respiratory chain complexes using cardiomyocyte SMP. BCPP compounds inhibited the binding of 3 H-dihydrorotenone to MC-I and the proton pumping activity of MC-I in a concentration-dependent manner in vitro...
March 18, 2018: Mitochondrion
María M Adeva-Andany, Natalia Carneiro-Freire, Mónica Seco-Filgueira, Carlos Fernández-Fernández, David Mouriño-Bayolo
Mitochondrial β-oxidation of fatty acids generates acetyl-coA, NADH and FADH2 . Acyl-coA synthetases catalyze the binding of fatty acids to coenzyme A to form fatty acyl-coA thioesters, the first step in the intracellular metabolism of fatty acids. l-carnitine system facilitates the transport of fatty acyl-coA esters across the mitochondrial membrane. Carnitine palmitoyltransferase-1 transfers acyl groups from coenzyme A to l-carnitine, forming acyl-carnitine esters at the outer mitochondrial membrane. Carnitine acyl-carnitine translocase exchanges acyl-carnitine esters that enter the mitochondria, by free l-carnitine...
March 15, 2018: Mitochondrion
Sirithip Chuaijit, Worawit Boonyatistan, Pichsinee Boonchuay, Chanatip Metheetrairut, Wichit Suthammarak
Assembly of complex I of the mitochondrial respiratory chain (MRC) requires not only structural subunits for electron transport, but also assembly factors. In the nematode Caenorhabditis elegans, NUAF-1 and NUAF-3 are the only two assembly factors that have been characterized. In this study, we identify ACDH-12 as an assembly factor of the respiratory complex I. We demonstrate for the first time that a deficiency of ACDH-12 affects the formation and function of complex I. RNAi knockdown of acdh-12 also shortens lifespan and decreases fecundity...
March 11, 2018: Mitochondrion
Mark A Tarnopolsky, Arun N E Sundaram, John Provias, Lauren Brady, Bekim Sadikovic
Two patients with an m.8340G>A mitochondrial DNA variant have been reported with one patient showing ptosis, ophthalmoparesis and myopathy at 53% heteroplasmy and another with pigmentary retinopathy, cataracts and sensory neural deafness and slightly higher heteroplasmy (65%). Here we report that higher muscle mutant heteroplasmy (93%) for m.8340G>A is associated with ptosis, ophthalmoparesis and mitochondrial myopathy, thus confirming the initial phenotypic association and showing that heteroplasmy per se does not explain the phenotypic spectrum of disease associated with the m...
March 6, 2018: Mitochondrion
Hitendra S Solanki, Niraj Babu, Ankit P Jain, Mohd Younis Bhat, Vinuth N Puttamallesh, Jayshree Advani, Remya Raja, Kiran K Mangalaparthi, Mahesh M Kumar, T S Keshava Prasad, Premendu Prakash Mathur, David Sidransky, Harsha Gowda, Aditi Chatterjee
Cellular transformation owing to cigarette smoking is due to chronic exposure and not acute. However, systematic studies to understand the molecular alterations in lung cells due to cigarette smoke are lacking. To understand these molecular alterations induced by chronic cigarette smoke exposure, we carried out tandem mass tag (TMT) based temporal proteomic profiling of lung cells exposed to cigarette smoke for upto 12months. We identified 2620 proteins in total, of which 671 proteins were differentially expressed (1...
May 2018: Mitochondrion
Jessica L Fetterman, Chunyu Liu, Gary F Mitchell, Ramachandran S Vasan, Emelia J Benjamin, Joseph A Vita, Naomi M Hamburg, Daniel Levy
Mitochondrial genetic variation with resultant alterations in oxidative phosphorylation may influence vascular function and contribute to cardiovascular disease susceptibility. We assessed relations of peptide-encoding variants in the mitochondrial genome with measures of vascular function in Framingham Heart Study participants. Of 258 variants assessed, 40 were predicted to have functional consequences by bioinformatics programs. A maternal pattern of heritability was estimated to contribute to the variability of aortic stiffness...
May 2018: Mitochondrion
Young Joon Kwon, Sujay Guha, Florin Tuluc, Marni J Falk
Mitochondrial respiratory chain disease is caused by a wide range of individually rare genetic disorders that impair cellular energy metabolism. While fluorescence microscopy analysis of nematodes fed MitoTracker Green (MTG) and tetramethylrhodamine ethyl ester (TMRE) can reliably quantify relative mitochondrial density and membrane potential, respectively, in C. elegans models of mitochondrial dysfunction, it is a tedious process with limitations in the number and age of animals that can be studied. A novel, large particle, flow cytometry-based method reported here accelerates and automates the relative quantitation of mitochondrial physiology in nematode populations...
May 2018: Mitochondrion
Agostinho G Rocha, Simon A B Knight, Alok Pandey, Heeyong Yoon, Jayashree Pain, Debkumar Pain, Andrew Dancis
The cysteine desulfurase Nfs1/Isd11 uses the amino acid cysteine as the substrate and its activity is absolutely required for contributing persulfide sulfur to the essential process of iron-sulfur (Fe-S) cluster assembly in mitochondria. Here we describe a novel regulatory process involving phosphorylation of Nfs1 in mitochondria. Phosphorylation enhanced cysteine desulfurase activity, while dephosphorylation decreased its activity. Nfs1 phosphopeptides were identified, and the corresponding phosphosite mutants showed impaired persulfide formation...
May 2018: Mitochondrion
Claudia Einer, Simon Hohenester, Ralf Wimmer, Lena Wottke, Renate Artmann, Sabine Schulz, Christian Gosmann, Alisha Simmons, Christin Leitzinger, Carola Eberhagen, Sabine Borchard, Sabine Schmitt, Stefanie M Hauck, Christine von Toerne, Martin Jastroch, Ellen Walheim, Christian Rust, Alexander L Gerbes, Bastian Popper, Doris Mayr, Max Schnurr, Angelika M Vollmar, Gerald Denk, Hans Zischka
Western lifestyle-associated malnutrition causes steatosis that may progress to liver inflammation and mitochondrial dysfunction has been suggested as a key factor in promoting this disease. Here we have molecularly, biochemically and biophysically analyzed mitochondria from steatotic wild type and immune-compromised mice fed a Western diet (WD) - enriched in saturated fatty acids (SFAs). WD-mitochondria demonstrated lipidomic changes, a decreased mitochondrial ATP production capacity and a significant sensitivity to calcium...
May 2018: Mitochondrion
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