ALBERT

Description:    Tuberculosis, caused by the strain Mycobacterium tuberculosis , is in focus of interest due to the emergence of multi- and extensive drug-resistant TB strains. The F 1 F O ATP synthase is one of the essential enzymes in energy requirement of both proliferating aerobic and hypoxic dormant stage of mycobacterium life cycle, and therefore a potential TB drug target. Subunit γ of F-ATP synthases plays an important role in coupling and catalysis via conformational transitions of its N- and C-termini as well as the bottom segment of the globular domain of γ, which is in close proximity to the rotating and ion-pumping c -ring. Here we describe the first production, purification and low resolution solution structure of subunit γ (γ 1–204 , Mt γ 1–204 ) of the M. tuberculosis F-ATP synthase. Mt γ 1–204 is a pear-like shaped protein with a molecular weight of 23 ± 2 kDa. Protein sequence analysis of Mt γ revealed differences in the amino acid composition to γ subunits from other sources, in particular the presence of a unique stretch of 13 amino acid residues ( Mt γ 165–178 ). NMR studies showed that Mt γ 165–178 forms a loop of polar residues. Mt γ 165–178 has been aligned at the bottom of the globular domain of the Escherichia coli subunit γ, being in close vicinity to the polar residues R41, Q42, E44 and Q46 ( M. tuberculosis nomenclature) of the c -ring. The putative role(s) of Mt γ 165–178 in coupling and as a potential drug target are discussed. Content Type Journal Article Pages 1-9 DOI 10.1007/s10863-012-9486-4 Authors Ragunathan Priya, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551 Republic of Singapore Goran Biuković, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551 Republic of Singapore Malathy Sony Subramanian Manimekalai, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551 Republic of Singapore Jackwee Lim, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551 Republic of Singapore Srinivasa P. S. Rao, Novartis Institute for Tropical Diseases, 10 Biopolis Road, 05‐01 Chromos, Singapore, 138670 Republic of Singapore Gerhard Grüber, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551 Republic of Singapore Journal Journal of Bioenergetics and Biomembranes Online ISSN 1573-6881 Print ISSN 0145-479X

Description: Erratum to: Experimental results using 3-bromopyruvate in mesothelioma: in vitro and in vivo studies Content Type Journal Article Category Erratum Pages 1-1 DOI 10.1007/s10863-012-9484-6 Authors Philippe Icard, Service de Chirurgie Thoracique, Centre Hospitalier Universitaire de Caen Basse-Normandie, Avenue de la Côte de Nacre, Caen, 14000 France Xiao-Dong Zhang, Université de Caen Basse-Normandie, EA 4656, Unité BioTICLA “Biologie et Thérapies Innovantes des Cancers Localement Agressifs”, Centre de Lutte Contre le Cancer François Baclesse, Av du général Harris, BP5026, 14076 Caen Cedex 05, France Edwige Lemoisson, Université de Caen Basse-Normandie, EA 4656, Unité BioTICLA “Biologie et Thérapies Innovantes des Cancers Localement Agressifs”, Centre de Lutte Contre le Cancer François Baclesse, Av du général Harris, BP5026, 14076 Caen Cedex 05, France Marie-Hélène Louis, Université de Caen Basse-Normandie, EA 4656, Unité BioTICLA “Biologie et Thérapies Innovantes des Cancers Localement Agressifs”, Centre de Lutte Contre le Cancer François Baclesse, Av du général Harris, BP5026, 14076 Caen Cedex 05, France Stéphane Allouche, Université de Caen Basse-Normandie, Laboratoire de biologie moléculaire et cellulaire de la signalisation, UPRES EA 3919, IFR 146 ICORE, 14032 Caen cedex, France Hubert Lincet, Université de Caen Basse-Normandie, EA 4656, Unité BioTICLA “Biologie et Thérapies Innovantes des Cancers Localement Agressifs”, Centre de Lutte Contre le Cancer François Baclesse, Av du général Harris, BP5026, 14076 Caen Cedex 05, France Laurent Poulain, Université de Caen Basse-Normandie, EA 4656, Unité BioTICLA “Biologie et Thérapies Innovantes des Cancers Localement Agressifs”, Centre de Lutte Contre le Cancer François Baclesse, Av du général Harris, BP5026, 14076 Caen Cedex 05, France Journal Journal of Bioenergetics and Biomembranes Online ISSN 1573-6881 Print ISSN 0145-479X

Description: Erratum to: The mitochondrial oxoglutarate carrier: from identification to mechanism Content Type Journal Article Category Erratum Pages 1-1 DOI 10.1007/s10863-012-9487-3 Authors Magnus Monné, Department of Biosciences, Biotechnology and Pharmacological Sciences, Laboratory of Biochemistry and Molecular Biology, University of Bari, Via E. Orabona 4, 70125 Bari, Italy Daniela Valeria Miniero, Department of Biosciences, Biotechnology and Pharmacological Sciences, Laboratory of Biochemistry and Molecular Biology, University of Bari, Via E. Orabona 4, 70125 Bari, Italy Vito Iacobazzi, Department of Biosciences, Biotechnology and Pharmacological Sciences, Laboratory of Biochemistry and Molecular Biology, University of Bari, Via E. Orabona 4, 70125 Bari, Italy Faustino Bisaccia, Department of Sciences, University of Basilicata, Via Ateneo Lucano 10, 85100 Potenza, Italy Giuseppe Fiermonte, Department of Biosciences, Biotechnology and Pharmacological Sciences, Laboratory of Biochemistry and Molecular Biology, University of Bari, Via E. Orabona 4, 70125 Bari, Italy Journal Journal of Bioenergetics and Biomembranes Online ISSN 1573-6881 Print ISSN 0145-479X

Description:    The aim of this study was to analyze quantitatively cellular respiration in intraoperational tissue samples taken from human breast cancer (BC) patients. We used oxygraphy and the permeabilized cell techniques in combination with Metabolic Control Analysis (MCA) to measure a corresponding flux control coefficient (FCC). The activity of all components of ATP synthasome, and respiratory chain complexes was found to be significantly increased in human BC cells in situ as compared to the adjacent control tissue. FCC(s) were determined upon direct activation of respiration with exogenously-added ADP and by titrating the complexes with their specific inhibitors to stepwise decrease their activity. MCA showed very high sensitivity of all complexes and carriers studied in human BC cells to inhibition as compared to mitochondria in normal oxidative tissues. The sum of FCC(s) for all ATP synthasome and respiratory chain components was found to be around 4, and the value exceeded significantly that for normal tissue (close to 1). In BC cells, the key sites of the regulation of respiration are Complex IV (FCC = 0.74), ATP synthase (FCC = 0.61), and phosphate carrier (FCC = 0.60); these FCC(s) exceed considerably (~10-fold) those for normal oxidative tissues. In human BC cells, the outer mitochondrial membrane is characterized by an increased permeability towards adenine nucleotides, the mean value of the apparent K m for ADP being equal to 114.8 ± 13.6 μM. Our data support the two-compartment hypothesis of tumor metabolism, the high sum of FCC(s) showing structural and functional organization of mitochondrial respiratory chain and ATP synthasome as supercomplexes in human BC. Content Type Journal Article Pages 1-20 DOI 10.1007/s10863-012-9457-9 Authors Tuuli Kaambre, Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, Tallinn, Estonia Vladimir Chekulayev, Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, Tallinn, Estonia Igor Shevchuk, Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, Tallinn, Estonia Minna Karu-Varikmaa, Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, Tallinn, Estonia Natalja Timohhina, Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, Tallinn, Estonia Kersti Tepp, Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, Tallinn, Estonia Jelena Bogovskaja, Clinic of Diagnostics at the North Estonia Medical Centre, Tallinn, Estonia Riina Kütner, Clinic of Surgery at the North Estonia Medical Centre, Tallinn, Estonia Vahur Valvere, Oncology and Hematology Clinic at the North Estonia Medical Centre, Tallinn, Estonia Valdur Saks, Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, Tallinn, Estonia Journal Journal of Bioenergetics and Biomembranes Online ISSN 1573-6881 Print ISSN 0145-479X

Description:    Cellular redox states can regulate cell metabolism, growth, differentiation, motility, apoptosis, signaling pathways, and gene expressions etc. A growing body of literature suggest the importance of redox status for cancer progression. While most studies on redox state were done on cells and tissue lysates, it is important to understand the role of redox state in a tissue in vivo/ex vivo and image its heterogeneity. Redox scanning is a clinical-translatable method for imaging tissue mitochondrial redox potential with a submillimeter resolution. Redox scanning data in mouse models of human cancers demonstrate a correlation between mitochondrial redox state and tumor metastatic potential. I will discuss the significance of this correlation and possible directions for future research. Content Type Journal Article Category MINI-REVIEW Pages 1-9 DOI 10.1007/s10863-012-9469-5 Authors Lin Z. Li, Molecular Imaging Laboratory, Department of Radiology, Britton Chance Laboratory of Redox Imaging, Johnson Research Foundation, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Journal Journal of Bioenergetics and Biomembranes Online ISSN 1573-6881 Print ISSN 0145-479X

Description:    Mitochondria have an essential role in powering cells by generating ATP following the metabolism of pyruvate derived from glycolysis. They are also the major source of generating reactive oxygen species (ROS), which have regulatory roles in cell death and proliferation. Mutations in mitochondrial DNA (mtDNA) and dysregulation of mitochondrial metabolism have been frequently described in human tumors. Although the role of oxidative stress as the consequence of mtDNA mutations and/or altered mitochondrial functions has been demonstrated in carciongenesis, a causative role of mitochondria in tumor progression has only been demonstrated recently. Specifically, the subject of this mini-review focuses on the role of mitochondria in promoting cancer metastasis. Cancer relapse and the subsequent spreading of cancer cells to distal sites are leading causes of morbidity and mortality in cancer patients. Despite its clinical importance, the underlying mechanisms of metastasis remain to be elucidated. Recently, it was demonstrated that mitochondrial oxidative stress could actively promote tumor progression and increase the metastatic potential of cancer cells. The purpose of this mini-review is to summarize current investigations of the roles of mitochondria in cancer metastasis. Future development of diagnostic and therapeutic strategies for patients with advanced cancer will benefit from the new knowledge of mitochondrial metabolism in epithelial cancer cells and the tumor stroma. Content Type Journal Article Category MINI-REVIEW Pages 1-4 DOI 10.1007/s10863-012-9465-9 Authors Emily I. Chen, Department Of Pharmacological Sciences & Proteomics Center School Of Medicine, Stony Brook University, BST 8-125, Stony Brook, NY 11794-8651, USA Journal Journal of Bioenergetics and Biomembranes Online ISSN 1573-6881 Print ISSN 0145-479X

Description:    The C-terminus (CT) of rCx46 consists of 186 residues (H230-I416). Recent studies showed that rCx46 28.2 , truncated after H243, altered the formation of functional hemichannels when expressed in Xenopus oocytes, while rCx46 37.7 , truncated after A333 formed gap junction hemichannels similarly to rCx46 wt . To analyze the role of the CT up to A333 in functional expression with cell imaging and dye-transfer techniques, different mutants were generated by C-terminal truncation between H243-A333, labeled with EGFP and expressed in HeLa cells. These rCx46 variants were characterized according to their compartmentalization in organelles, their presence in microscopic detectable vesicles and their ability to form gap junction plaques. rCx46 truncated after A311 (rCx46 35.3 ) was compartmentalized, was found in vesicles and formed functional gap junction plaques similarly to rCx46 wt . With a truncation after P284 (rCx46 32.6 ), the protein was not compartmentalized and the amount of vesicles containing the protein were reduced; however, functional gap junction plaque formation was not affected as compared to rCx46 35.3 . rCx46 28.2 did not form functional gap junction plaques; it was not found in vesicles or in cellular compartments. Live-cell imaging and detection of annular junctions for rCx46 32.6 and rCx46 35.3 revealed that the truncation after P284 reduced the frequency of vesicle budding from gap junction plaques and the formation of annular junctions. These results suggest that the C-terminal region of rCx46 up to A311 (rCx46 35.3 ) is necessary for its correct compartmentalization and internalization in the form of annular junctions, while the H230-P284 C-terminal region (rCx46 32.6 ) is sufficient for the formation of dye coupled gap junction channels. Content Type Journal Article Pages 1-12 DOI 10.1007/s10863-012-9480-x Authors Barbara Schlingmann, Institute of Biophysics, Leibniz University Hannover, Herrenhäuserstr. 2, 30419 Hannover, Germany Patrik Schadzek, Institute of Biophysics, Leibniz University Hannover, Herrenhäuserstr. 2, 30419 Hannover, Germany Franziska Hemmerling, Institute of Biophysics, Leibniz University Hannover, Herrenhäuserstr. 2, 30419 Hannover, Germany Frank Schaarschmidt, Institute of Biostatistics, Leibniz University Hannover, Herrenhäuserstr. 2, 30419 Hannover, Germany Alexander Heisterkamp, Institute of applied Optics, Friedrich-Schiller-Universityt-Jena, Froebelstieg 1, 07743 Jena, Germany Anaclet Ngezahayo, Institute of Biophysics, Leibniz University Hannover, Herrenhäuserstr. 2, 30419 Hannover, Germany Journal Journal of Bioenergetics and Biomembranes Online ISSN 1573-6881 Print ISSN 0145-479X

Description: Erratum to: Prerequisites for ubiquinone analogs to prevent mitochondrial permeability transition-induced cell death Content Type Journal Article Category Erratum Pages 1-1 DOI 10.1007/s10863-012-9434-3 Authors Julie Belliere, Inserm, U1055, Grenoble, 38041 France Flavien Devun, Inserm, U1055, Grenoble, 38041 France Cécile Cottet-Rousselle, Inserm, U1055, Grenoble, 38041 France Cécile Batandier, Inserm, U1055, Grenoble, 38041 France Xavier Leverve, Inserm, U1055, Grenoble, 38041 France Eric Fontaine, Inserm, U1055, Grenoble, 38041 France Journal Journal of Bioenergetics and Biomembranes Online ISSN 1573-6881 Print ISSN 0145-479X

Description:    Biosynthesis of nucleoside triphosphates is critical for bioenergetics and nucleic acid replication, and this is achieved by nucleoside diphosphate kinase (NDK). As an emerging biological model and the global importance of shrimp culture, we have addressed the study of the Pacific whiteleg shrimp ( Litopenaeus vannamei ) NDK. We demonstrated its activity and affinity towards deoxynucleoside diphosphates. Also, the quaternary structure obtained by gel filtration chromatography showed that shrimp NDK is a trimer. Affinity was in the micro-molar range for dADP, dGDP, dTDP and except for dCDP, which presented no detectable interaction by isothermal titration calorimetry, as described previously for Plasmodium falciparum NDK. This information is particularly important, as this enzyme could be used to test nucleotide analogs that can block white spot syndrome virus (WSSV) viral replication and to study its bioenergetics role during hypoxia and fasting. Content Type Journal Article Pages 1-7 DOI 10.1007/s10863-012-9436-1 Authors Idania E. Quintero-Reyes, Aquatic Molecular Biology Lab, Centro de Investigación en Alimentación y Desarrollo A.C., Carretera a Ejido la Victoria Km 0.6, Hermosillo, Sonora 83304, Mexico Karina D. Garcia-Orozco, Aquatic Molecular Biology Lab, Centro de Investigación en Alimentación y Desarrollo A.C., Carretera a Ejido la Victoria Km 0.6, Hermosillo, Sonora 83304, Mexico Rocio Sugich-Miranda, Aquatic Molecular Biology Lab, Centro de Investigación en Alimentación y Desarrollo A.C., Carretera a Ejido la Victoria Km 0.6, Hermosillo, Sonora 83304, Mexico Aldo A. Arvizu-Flores, Department of Chemical Biological Sciences, Universidad de Sonora, Rosales y Blvd. Luis Encinas s/num, Hermosillo, Sonora 83000, Mexico Enrique F. Velazquez-Contreras, Department of Polymer Science and Materials, Universidad de Sonora, Rosales y Blvd. Luis Encinas s/num, Hermosillo, Sonora 83000, Mexico Francisco J. Castillo-Yañez, Department of Chemical Biological Sciences, Universidad de Sonora, Rosales y Blvd. Luis Encinas s/num, Hermosillo, Sonora 83000, Mexico Rogerio R. Sotelo-Mundo, Centro de Investigación en Alimentación y Desarrollo A.C., Carretera a Ejido la Victoria Km 0.6, Hermosillo, Sonora 83304, Mexico Journal Journal of Bioenergetics and Biomembranes Online ISSN 1573-6881 Print ISSN 0145-479X

Description:    Blood vessel dilation starts from activation of the Na/K pumps and inward rectifier K channels in the vessel smooth muscle cells, which hyperpolarizes the cell membrane potential and closes the Ca channels. As a result, the intracellular Ca concentration reduces, and the smooth muscle cells relax and the blood vessel dilates. Activation of the Na/K pumps and the membrane potential hyperpolarization plays a critical role in blood vessel functions. Previously, we developed a new technique, synchronization modulation, to control the pump functions by electrically entraining the pump molecules. We have applied the synchronization modulation electric field noninvasively to various intact cells and demonstrated the field-induced membrane potential hyperpolarization. We further applied the electric field to blood vessels and investigated the field induced functional changes of the vessels. In this paper, we report the results in a study of the membrane potential change in the smooth muscle cells of mesenteric blood vessels in response to the oscillating electric field. We found that the synchronization modulation electric field can effectively hyperpolarize the muscle membrane potential quickly in seconds under physiological conditions. Content Type Journal Article Pages 1-11 DOI 10.1007/s10863-012-9432-5 Authors Liping Zhang, Cellular and Molecular Biophysics Lab, Department of Physics, University of South Florida, Tampa, FL 33620, USA Zhihui Fang, Cellular and Molecular Biophysics Lab, Department of Physics, University of South Florida, Tampa, FL 33620, USA Wei Chen, Cellular and Molecular Biophysics Lab, Department of Physics, University of South Florida, Tampa, FL 33620, USA Journal Journal of Bioenergetics and Biomembranes Online ISSN 1573-6881 Print ISSN 0145-479X