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https://www.readbyqxmd.com/read/28342810/expression-and-putative-role-of-mitochondrial-transport-proteins-in-cancer
#1
REVIEW
Oleksandr Lytovchenko, Edmund R S Kunji
Cancer cells undergo major changes in energy and biosynthetic metabolism. One of them is the Warburg effect, in which pyruvate is used for fermentation rather for oxidative phosphorylation. Another major one is their increased reliance on glutamine, which helps to replenish the pool of Krebs cycle metabolites used for other purposes, such as amino acid or lipid biosynthesis. Mitochondria are central to these alterations, as the biochemical pathways linking these processes run through these organelles. Two membranes, an outer and inner membrane, surround mitochondria, the latter being impermeable to most organic compounds...
March 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28342809/identity-and-function-of-a-cardiac-mitochondrial-small-conductance-ca-2-activated-k-channel-splice-variant
#2
Meiying Yang, Amadou K S Camara, Mohammed Aldakkak, Wai-Meng Kwok, David F Stowe
We provide evidence for location and function of a small conductance, Ca(2+)-activated K(+) (SKCa) channel isoform 3 (SK3) in mitochondria (m) of guinea pig, rat and human ventricular myocytes. SKCa agonists protected isolated hearts and mitochondria against ischemia/reperfusion (IR) injury; SKCa antagonists worsened IR injury. Intravenous infusion of a SKCa channel agonist/antagonist, respectively, in intact rats was effective in reducing/enhancing regional infarct size induced by coronary artery occlusion...
March 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28338658/granzyme-b-enters-the-mitochondria-in-a-sam50-tim22-and-mthsp70-dependent-manner-to-induce-apoptosis
#3
Valentina Chiusolo, Guillaume Jacquemin, Esen Yonca Bassoy, Laurent Vinet, Lavinia Liguori, Michael Walch, Vera Kozjak-Pavlovic, Denis Martinvalet
We have found that granzyme B (GB)-induced apoptosis also requires reactive oxygen species resulting from the alteration of mitochondrial complex I. How GB, which does not possess a mitochondrial targeting sequence, enter this organelle is unknown. We show that GB enters the mitochondria independently of the translocase of the outer mitochondrial membrane complex, but requires instead Sam50, the central subunit of the sorting and assembly machinery that integrates outer membrane β-barrel proteins. Moreover, GB breaches the inner membrane through Tim22, the metabolite carrier translocase pore, in a mitochondrial heat-shock protein 70 (mtHsp70)-dependent manner...
March 24, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28336315/cardiolipin-and-mitochondrial-cristae-organization
#4
REVIEW
Nikita Ikon, Robert O Ryan
A fundamental question in cell biology, under investigation for over six decades, is the structural organization of mitochondrial cristae. Long known to harbor electron transport chain proteins, crista membrane integrity is key to establishment of the proton gradient that drives oxidative phosphorylation. Visualization of cristae morphology by electron microscopy / tomography has provided evidence that cristae are tube-like extensions of the mitochondrial inner membrane (IM) that project into the matrix space...
March 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28333438/nuclear-membrane-targeted-gold-nanoparticles-inhibit-cancer-cell-migration-and-invasion
#5
Moustafa R K Ali, Yue Wu, Deepraj Ghosh, Brian H Do, Kuangcai Chen, Michelle R Dawson, Ning Fang, Todd A Sulchek, Mostafa A El-Sayed
Most cancer patients die from metastasis. Recent studies have shown that gold nanoparticles (AuNPs) can slow down the migration/invasion speed of cancer cells and suppress metastasis. Since nuclear stiffness of the cell largely decreases cell migration, our hypothesis is that targeting AuNPs to the cell nucleus region could enhance nuclear stiffness, and therefore inhibit cell migration and invasion. Our results showed that upon nuclear targeting of AuNPs, the ovarian cancer cell motilities decrease significantly, compared with nontargeted AuNPs...
March 27, 2017: ACS Nano
https://www.readbyqxmd.com/read/28333095/cytosolic-bnip3-dimer-interacts-with-mitochondrial-bax-forming-heterodimers-in-the-mitochondrial-outer-membrane-under-basal-conditions
#6
Ulrike B Hendgen-Cotta, Sonja Esfeld, Katharina Rudi, Ilkka Miinalainen, Johann P Klare, Tienush Rassaf
The primary function of mitochondria is energy production, a task of particular importance especially for cells with a high energy demand like cardiomyocytes. The B-cell lymphoma (BCL-2) family member BCL-2 adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) is linked to mitochondrial targeting after homodimerization, where it functions in inner membrane depolarization and permeabilization of the mitochondrial outer membrane (MOM) mediating cell death. We investigated the basal distribution of cardiac BNIP3 in vivo and its physical interaction with the pro-death protein BCL2 associated X, apoptosis regulator (BAX) and with mitochondria using immunoblot analysis, co-immunoprecipitation, and continuous wave and pulsed electron paramagnetic resonance spectroscopy techniques...
March 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28330871/human-mitochondrial-cytochrome-c-oxidase-assembly-factor-cox18-acts-transiently-as-a-membrane-insertase-within-the-subunit-2-maturation-module
#7
Myriam Bourens, Antoni Barrientos
Defects in mitochondrial cytochrome c oxidase or respiratory chain complex IV (CIV) assembly are a frequent cause of human mitochondrial disorders. Specifically, mutations in four conserved assembly factors impinging the biogenesis of the mitochondrion-encoded catalytic core subunit 2 (COX2) result in myopathies. These factors afford stability of newly-synthesized COX2 (the dystonia-ataxia syndrome protein COX20), a protein with two transmembrane domains, and maturation of its copper center CuA (cardiomyopathy proteins SCO1, SCO2 and COA6)...
March 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28329765/structural-insights-into-adiponectin-receptors-suggest-ceramidase-activity
#8
Ieva Vasiliauskaité-Brooks, Remy Sounier, Pascal Rochaix, Gaëtan Bellot, Mathieu Fortier, François Hoh, Luigi De Colibus, Chérine Bechara, Essa M Saied, Christoph Arenz, Cédric Leyrat, Sébastien Granier
Adiponectin receptors (ADIPORs) are integral membrane proteins that control glucose and lipid metabolism by mediating, at least in part, a cellular ceramidase activity that catalyses the hydrolysis of ceramide to produce sphingosine and a free fatty acid (FFA). The crystal structures of the two receptor subtypes, ADIPOR1 and ADIPOR2, show a similar overall seven-transmembrane-domain architecture with large unoccupied cavities and a zinc binding site within the seven transmembrane domain. However, the molecular mechanisms by which ADIPORs function are not known...
March 22, 2017: Nature
https://www.readbyqxmd.com/read/28327712/structural-transformation-of-vesicles-formed-by-a-polystyrene-b-poly-acrylic-acid-polystyrene-b-poly-4-vinyl-pyridine-mixture-from-symmetric-to-asymmetric-membranes
#9
Zhen Geng, Yuanyuan Han, Wei Jiang
Asymmetric vesicles with different inner and outer corona compositions are applicable in microreactors, drug delivery, and biomimics because of their unique functions in membrane permeability and protein localization. In this study, we develop a novel approach to construct asymmetric vesicles and demonstrate the first structural transformation of polymeric vesicles from symmetric to asymmetric membranes. Experimental results and Monte Carlo simulation results clearly reveal that increased intercorona repulsion and enhanced hydrophobic chain mobility are essential to realize this transformation...
March 22, 2017: Soft Matter
https://www.readbyqxmd.com/read/28325042/enhanced-endosomal-escape-by-light-fueled-liquid-metal-transformer
#10
Yue Lu, Yiliang Lin, Zhaowei Chen, Quanyin Hu, Yang Liu, Shuangjiang Yu, Wei Gao, Michael D Dickey, Zhen Gu
Effective endosomal escape remains as the "holy grail" for endocytosis-based intracellular drug delivery. To date, most of the endosomal escape strategies rely on small molecules, cationic polymers, or pore-forming proteins, which are often limited by the systemic toxicity and lack of specificity. We describe here a light-fueled liquid-metal transformer for effective endosomal escape-facilitated cargo delivery via a chemical-mechanical process. The nanoscale transformer can be prepared by a simple approach of sonicating a low-toxicity liquid-metal...
March 22, 2017: Nano Letters
https://www.readbyqxmd.com/read/28317877/transcription-factor-nf-kappa-b-represses-ant1-transcription-and-leads-to-mitochondrial-dysfunctions
#11
Chen Zhang, Hui Jiang, Pin Wang, Heng Liu, Xiulian Sun
Mitochondria are intracellular organelles involved in cell survival and death, and dysfunctions of mitochondria are related to neurodegenerative diseases. As the most abundant protein in the mitochondrial inner membrane, adenine nucleotide translocator 1 (ANT1) plays a critical role in mitochondrial function, including the exchange of adenosine triphosphate/adenosine diphosphate (ATP/ADP) in mitochondria, basal proton leak and mitochondrial permeability transition pore (mPTP). Here, we show that ANT1 transcription is regulated by transcription factor NF-kappa B (NF-κB)...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298442/the-short-variant-of-the-mitochondrial-dynamin-opa1-maintains-mitochondrial-energetics-and-cristae-structure
#12
Hakjoo Lee, Sylvia B Smith, Yisang Yoon
The protein optic atrophy 1 (OPA1) is a dynamin-related protein associated with the inner mitochondrial membrane, and functions in mitochondrial inner membrane fusion and cristae maintenance. Inner membrane-anchored long OPA1 (L-OPA1) undergoes proteolytic cleavage resulting in short OPA1 (S-OPA1). It is often thought that S-OPA1 is a functionally insignificant proteolytic product of L-OPA1 because the accumulation of S-OPA1 due to L-OPA1 cleavage is observed in mitochondrial fragmentation and dysfunction. However, cells contain a mixture of both L- and S-OPA1 in normal conditions, suggesting the functional significance of maintaining both OPA1 forms, but the differential roles of L- and S-OPA1 in mitochondrial fusion and energetics are ill-defined...
March 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28297675/unconventional-targeting-of-a-thiol-peroxidase-to-the-mitochondrial-intermembrane-space-facilitates-oxidative-protein-folding
#13
Paraskevi Kritsiligkou, Afroditi Chatzi, Georgia Charalampous, Aleksandr Mironov, Chris M Grant, Kostas Tokatlidis
Thiol peroxidases are conserved hydrogen peroxide scavenging and signaling molecules that contain redox-active cysteine residues. We show here that Gpx3, the major H2O2 sensor in yeast, is present in the mitochondrial intermembrane space (IMS), where it serves a compartment-specific role in oxidative metabolism. The IMS-localized Gpx3 contains an 18-amino acid N-terminally extended form encoded from a non-AUG codon. This acts as a mitochondrial targeting signal in a pathway independent of the hitherto known IMS-import pathways...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28295037/a-mutation-in-the-tmem65-gene-results-in-mitochondrial-myopathy-with-severe-neurological-manifestations
#14
Aisha Nazli, Adeel Safdar, Ayesha Saleem, Mahmood Akhtar, Lauren I Brady, Jeremy Schwartzentruber, Mark A Tarnopolsky
Recent research has suggested that transmembrane protein 65 (TMEM65) is localized within the inner mitochondrial membrane. Little else is known about its function. In this study we investigated the location and function of TMEM65. Further, we report the functional consequences of a novel homozygous splice variant (c.472+1G>A) in the TMEM65 gene in a patient with mitochondrial encephalomyopathy. Here we investigated the location of TMEM65 by immunofluorescence staining of the protein and by immunoblotting of the isolated mitochondrial fractions in healthy fibroblasts and those from the patient...
March 15, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28291804/purification-of-cone-outer-segment-for-proteomic-analysis-on-its-membrane-proteins-in-carp-retina
#15
Takashi Fukagawa, Kazuaki Takafuji, Shuji Tachibanaki, Satoru Kawamura
Rods and cones are both photoreceptors in the retina, but they are different in many aspects including the light response characteristics and, for example, cell morphology and metabolism. These differences would be caused by differences in proteins expressed in rods and cones. To understand the molecular bases of these differences between rods and cones, one of the ways is to compare proteins expressed in rods and cones, and to find those expressed specifically or dominantly. In the present study, we are interested in proteins in the outer segment (OS), the site responsible for generation of rod- or cone-characteristic light responses and also the site showing different morphology between rods and cones...
2017: PloS One
https://www.readbyqxmd.com/read/28289229/persistence-of-the-mitochondrial-permeability-transition-in-the-absence-of-subunit-c-of-human-atp-synthase
#16
Jiuya He, Holly C Ford, Joe Carroll, Shujing Ding, Ian M Fearnley, John E Walker
The permeability transition in human mitochondria refers to the opening of a nonspecific channel, known as the permeability transition pore (PTP), in the inner membrane. Opening can be triggered by calcium ions, leading to swelling of the organelle, disruption of the inner membrane, and ATP synthesis, followed by cell death. Recent proposals suggest that the pore is associated with the ATP synthase complex and specifically with the ring of c-subunits that constitute the membrane domain of the enzyme's rotor...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28288130/parl-mediates-smac-proteolytic-maturation-in-mitochondria-to-promote-apoptosis
#17
Shotaro Saita, Hendrik Nolte, Kai Uwe Fiedler, Hamid Kashkar, A Saskia Venne, René P Zahedi, Marcus Krüger, Thomas Langer
Mitochondria drive apoptosis by releasing pro-apoptotic proteins that promote caspase activation in the cytosol. The rhomboid protease PARL, an intramembrane cleaving peptidase in the inner membrane, regulates mitophagy and plays an ill-defined role in apoptosis. Here, we employed PARL-based proteomics to define its substrate spectrum. Our data identified the mitochondrial pro-apoptotic protein Smac (also known as DIABLO) as a PARL substrate. In apoptotic cells, Smac is released into the cytosol and promotes caspase activity by inhibiting inhibitors of apoptosis (IAPs)...
March 13, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28288102/a-fret-sensor-enables-quantitative-measurements-of-membrane-charges-in-live-cells
#18
Yuanqing Ma, Yui Yamamoto, Philip R Nicovich, Jesse Goyette, Jérémie Rossy, J Justin Gooding, Katharina Gaus
Membrane charge has a critical role in protein trafficking and signaling. However, quantification of the effective electrostatic potential of cellular membranes has remained challenging. We developed a fluorescence membrane charge sensor (MCS) that reports changes in the membrane charge of live cells via Förster resonance energy transfer (FRET). MCS is permanently attached to the inner leaflet of the plasma membrane and shows a linear, reversible and fast response to changes of the electrostatic potential...
March 13, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28287172/killing-of-staphylococcus-aureus-and-salmonella-enteritidis-and-neutralization-of-lipopolysaccharide-by-17-residue-bovine-lactoferricins-improved-activity-of-trp-ala-containing-molecules
#19
Ya Hao, Na Yang, Xiumin Wang, Da Teng, Ruoyu Mao, Xiao Wang, Zhanzhan Li, Jianhua Wang
Bovine lactoferricin (LfcinB) has potent antibacterial, antifungal and antiparasitic activities but is also hemolytic. Our objective was to identify LfcinB17-31 derivatives with reduced hemolysis and improved antimicrobial activity via substituting Cys3, Arg4, Gln7, Met10, and Gly14 with more hydrophobic residues. Two peptides, Lfcin4 and Lfcin5, showed higher activity against Staphylococcus aureus and Salmonella enteritidis and lower hemolytic activity than the parent peptide LfcinB17-31. These peptides permeabilized the outer and inner membranes of S...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28283569/the-novel-chloroplast-outer-membrane-kinase-koc1-is-a-required-component-of-the-plastid-protein-import-machinery
#20
Mónica Zufferey, Cyrille Montandon, Véronique Douet, Emilie Demarsy, Birgit Agne, Sacha Baginsky, Felix Kessler
The biogenesis and maintenance of cell organelles such as mitochondria and chloroplasts requires the import of many proteins from the cytosol, a process that is controlled by phosphorylation. In the case of chloroplasts, the import of hundreds of different proteins depends on Translocons at the Outer and Inner Chloroplast membrane (TOC and TIC, respectively) complexes. The essential protein TOC159 functions thereby as an import receptor. It has an N-terminal acidic (A) domain that extends into the cytosol, controls receptor specificity, and is highly phosphorylated in vivo...
March 10, 2017: Journal of Biological Chemistry
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