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https://www.readbyqxmd.com/read/29343430/cardiolipin-synthesizing-enzymes-form-a-complex-that-interacts-with-cardiolipin-dependent-membrane-organizing-proteins
#1
Mauro Serricchio, Adriano Vissa, Peter K Kim, Christopher M Yip, G A McQuibban
The mitochondrial glycerophospholipid cardiolipin plays important roles in mitochondrial biology. Most notably, cardiolipin directly binds to mitochondrial proteins and helps assemble and stabilize mitochondrial multi-protein complexes. Despite their importance for mitochondrial health, how the proteins involved in cardiolipin biosynthesis are organized and embedded in mitochondrial membranes has not been investigated in detail. Here we show that human PGS1 and CLS1 are constituents of large protein complexes...
January 14, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29343244/hsp70-at-the-membrane-driving-protein-translocation
#2
REVIEW
Elizabeth A Craig
Efficient movement of proteins across membranes is required for cell health. The translocation process is particularly challenging when the channel in the membrane through which proteins must pass is narrow-such as those in the membranes of the endoplasmic reticulum and mitochondria. Hsp70 molecular chaperones play roles on both sides of these membranes, ensuring efficient translocation of proteins synthesized on cytosolic ribosomes into the interior of these organelles. The "import motor" in the mitochondrial matrix, which is essential for driving the movement of proteins across the mitochondrial inner membrane, is arguably the most complex Hsp70-based system in the cell...
January 17, 2018: BMC Biology
https://www.readbyqxmd.com/read/29342083/regulation-of-mitochondrial-dynamics-by-proteolytic-processing-and-protein-turnover
#3
REVIEW
Sumaira Ali, Gavin P McStay
The mitochondrial network is a dynamic organization within eukaryotic cells that participates in a variety of essential cellular processes, such as adenosine triphosphate (ATP) synthesis, central metabolism, apoptosis and inflammation. The mitochondrial network is balanced between rates of fusion and fission that respond to pathophysiologic signals to coordinate appropriate mitochondrial processes. Mitochondrial fusion and fission are regulated by proteins that either reside in or translocate to the inner or outer mitochondrial membranes or are soluble in the inter-membrane space...
January 17, 2018: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29339384/a-novel-inhibitor-of-the-lolcde-abc-transporter-essential-for-lipoprotein-trafficking-in-gram-negative-bacteria
#4
Nicholas N Nickerson, Christine C Jao, Yiming Xu, John Quinn, Elizabeth Skippington, Mary Kate Alexander, Anh Miu, Nicholas Skelton, Jessica V Hankins, Michael S Lopez, Christopher M Koth, Steven Rutherford, Mireille Nishiyama
The outer membrane is an essential structural component of Gram-negative bacteria that is composed of lipoproteins, lipopolysaccharides, phospholipids, and integral β-barrel membrane proteins. A dedicated machinery, called the Lol system, ensures proper trafficking of lipoproteins from the inner to the outer membrane. The LolCDE ABC transporter is the inner membrane component, which is essential for bacterial viability. Here, we report a novel pyrrolopyrimidinedione compound, G0507, which was identified in a phenotypic screen for inhibitors of E...
January 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29339082/water-mediated-interactions-enable-smooth-substrate-transport-in-a-bacterial-efflux-pump
#5
Attilio Vittorio Vargiu, Venkata Krishnan Ramaswamy, Ivana Malvacio, Giuliano Malloci, Ulrich Kleinekathöfer, Paolo Ruggerone
BACKGROUND: Efflux pumps of the Resistance-Nodulation-cell Division superfamily confer multi-drug resistance to Gram-negative bacteria. The most-studied polyspecific transporter belonging to this class is the inner-membrane trimeric antiporter AcrB of Escherichia coli. In previous studies, a functional rotation mechanism was proposed for its functioning, according to which the three monomers undergo concerted conformational changes facilitating the extrusion of substrates. However, the molecular determinants and the energetics of this mechanism still remain unknown, so its feasibility must be proven mechanistically...
January 12, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29338257/a-dynamic-protein-protein-coupling-between-the-tonb-dependent-transporter-fhua-and-tonb
#6
Jessica Sarver, Michael Zhang, Lishan Liu, David Nyenhuis, David S Cafiso
Bacterial outer membrane TonB-dependent transporters function by executing cycles of binding and unbinding to the inner membrane protein TonB. In the vitamin B12 transporter BtuB and the ferric citrate transporter FecA, substrate binding increases the periplasmic exposure of the Ton box, an energy-coupling segment. This increased exposure appears to enhance the affinity of the transporter for TonB. Here, continuous wave and pulse EPR spectroscopy were used to examine the state of the Ton box in the Escherichia coli ferrichrome transporter, FhuA...
January 17, 2018: Biochemistry
https://www.readbyqxmd.com/read/29338048/ebola-virus-requires-a-host-scramblase-for-externalization-of-phosphatidylserine-on-the-surface-of-viral-particles
#7
Asuka Nanbo, Junki Maruyama, Masaki Imai, Michiko Ujie, Yoichiro Fujioka, Shinya Nishide, Ayato Takada, Yusuke Ohba, Yoshihiro Kawaoka
Cell surface receptors for phosphatidylserine contribute to the entry of Ebola virus (EBOV) particles, indicating that the presence of phosphatidylserine in the envelope of EBOV is important for the internalization of EBOV particles. Phosphatidylserine is typically distributed in the inner layer of the plasma membrane in normal cells. Progeny virions bud from the plasma membrane of infected cells, suggesting that phosphatidylserine is likely flipped to the outer leaflet of the plasma membrane in infected cells for EBOV virions to acquire it...
January 16, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29337275/the-o-%C3%AE-linked-n-acetylglucosaminylation-of-the-lamin-b-receptor-and-its-impact-on-dna-binding-and-phosphorylation
#8
Caroline Smet-Nocca, Adeline Page, François-Xavier Cantrelle, Eleni Nikolakaki, Isabelle Landrieu, Thomas Giannakouros
Lamin B Receptor (LBR) is an integral protein of the interphase inner nuclear membrane that is implicated in chromatin anchorage to the nuclear envelope. Phosphorylation of a stretch of arginine-serine (RS) dipeptides in the amino-terminal nucleoplasmic domain of LBR regulates the interactions of the receptor with other nuclear proteins, DNA and RNA and thus modulates tethering of heterochromatin to the nuclear envelope. While phosphorylation has been extensively studied, very little is known about other post-translational modifications of the protein...
January 11, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29332576/current-understanding-of-physicochemical-mechanisms-for-cell-membrane-penetration-of-arginine-rich-cell-penetrating-peptides-role-of-glycosaminoglycan-interactions
#9
Yuki Takechi-Haraya, Hiroyuki Saito
Arginine-rich cell penetrating peptides (CPPs) are very promising drug carriers to deliver membrane-impermeable pharmaceuticals, such as siRNA, bioactive peptides and proteins. CPPs directly penetrate into cells across cell membranes via a spontaneous energy-independent process, in which CPPs appear to interact with acidic lipids in the outer leaflet of the cell membrane. However, acidic lipids represent only 10 to 20% of the total membrane lipid content and in mammalian cell membranes they are predominantly located in the inner leaflet...
January 11, 2018: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/29330316/myosin-1c-uses-a-novel-phosphoinositide-dependent-pathway-for-nuclear-localization
#10
Ilja Nevzorov, Ekaterina Sidorenko, Weihuan Wang, Hongxia Zhao, Maria K Vartiainen
Accurate control of macromolecule transport between nucleus and cytoplasm underlines several essential biological processes, including gene expression. According to the canonical model, nuclear import of soluble proteins is based on nuclear localization signals and transport factors. We challenge this view by showing that nuclear localization of the actin-dependent motor protein Myosin-1C (Myo1C) resembles the diffusion-retention mechanism utilized by inner nuclear membrane proteins. We show that Myo1C constantly shuttles in and out of the nucleus and that its nuclear localization does not require soluble factors, but is dependent on phosphoinositide binding...
January 12, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29329756/phospholipid-composition-of-the-outer-membrane-of-escherichia-coli-influences-its-susceptibility-against-antimicrobial-peptide-apidaecin-1b
#11
Rico Schmidt, Ding Yonghong, Ralf Hoffmann
Proline-rich antimicrobial peptides (PrAMPs) kill bacteria in a multimodal mechanism by inhibiting the 70S ribosome (i.e., protein translation) as dominant lethal mechanism besides inhibition of several other proteins, such as chaperone DnaK. PrAMPs pass the outer membrane of Gram-negative bacteria, probably by a self-promoted uptake followed by a transporter-mediated uptake from the periplasm. Mutation of transporter protein SbmA is a well-studied resistance mechanism observed in vitro by resistance induction with PrAMPs...
November 21, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29329746/evaluation-of-a-transtympanic-delivery-system-in-mus-musculus-for-extended-release-steroids
#12
Nathan H Dormer, Jennifer Nelson-Brantley, Hinrich Staecker, Cory J Berkland
OBJECTIVE: The current investigation evaluated a novel extended release delivery system for treating inner ear diseases. The platform technology consists of a film forming agent (FFA) and microsphere component to localize and extend drug delivery within the ear. STUDY DESIGN: Studies evaluated dissolution kinetics of microspheres with multiple encapsulates, testing of a variety of FFAs, and ability to localize to the round window membrane in mice in vivo. SETTING: Studies were completed at Orbis Biosciences and The University of Kansas Medical Center...
January 9, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29327420/expanding-the-phenotype-of-slc25a42-associated-mitochondrial-encephalomyopathy
#13
M Almannai, A Alsamri, A Alqasmi, E Faqeih, F AlMutairi, M Alotaibi, M M Samman, W Eyaid, Y I Aljadhai, H E Shamseldin, W Craigen, F S Alkuraya
SLC25A42 gene encodes an inner mitochondrial membrane protein that imports Co-enzyme A (CoA) into the mitochondrial matrix. A mutation in this gene was recently reported in a subject born to consanguineous parents who presented with mitochondrial myopathy with muscle weakness and lactic acidosis. In this report, we present 12 additional individuals with the same founder mutation who presented with variable manifestations ranging from asymptomatic lactic acidosis to a severe phenotype characterized by developmental regression and epilepsy...
January 12, 2018: Clinical Genetics
https://www.readbyqxmd.com/read/29327200/exocyst-complex-member-exoc5-is-required-for-survival-of-hair-cells-and-spiral-ganglion-neurons-and-maintenance-of-hearing
#14
Byeonghyeon Lee, Jeong-In Baek, Hyehyun Min, Seung-Hyun Bae, Kyeonghye Moon, Min-A Kim, Ye-Ri Kim, Ben Fogelgren, Joshua H Lipschutz, Kyu-Yup Lee, Jinwoong Bok, Un-Kyung Kim
The exocyst, an octameric protein complex consisting of Exoc1 through Exoc8, was first determined to regulate exocytosis by targeting vesicles to the plasma membrane in yeast to mice. In addition to this fundamental role, the exocyst complex has been implicated in other cellular processes. In this study, we investigated the role of the exocyst in cochlear development and hearing by targeting EXOC5, a central exocyst component. Deleting Exoc5 in the otic epithelium with widely used Cre lines resulted in early lethality...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29317431/suppression-of-activated-foxo-transcription-factors-in-the-heart-prolongs-survival-in-a-mouse-model-of-laminopathies
#15
Gaelle Auguste, Priyatansh Gurha, Raffaella Lombardi, Cristian Coarfa, James T Willerson, Ali J Marian
Rationale: Mutations in the LMNA gene, encoding nuclear inner membrane protein Lamin A/C, cause distinct phenotypes, collectively referred to as laminopathies. Heart failure, conduction defects, and arrhythmias are the common causes of death in laminopathies. Objective: To identify and therapeutically target the responsible mechanism(s) for cardiac phenotype in laminopathies. Methods and Results: Whole heart RNA sequencing was performed prior to the onset of cardiac dysfunction in the Lmna-/- and matched control mice...
January 9, 2018: Circulation Research
https://www.readbyqxmd.com/read/29315581/parkinson-disease-related-dj-1-modulates-the-expression-of-uncoupling-protein-4-against-oxidative-stress
#16
Shaoqing Xu, Xiaodong Yang, Yiwei Qian, Qin Xiao
Loss of function mutations of DJ-1 (PARK7) have been linked to the pathogenesis of Parkinson disease (PD). Antioxidative stress is one of the multi-protective functions of DJ-1, and oxidation of cysteine 106 (Cys106) has been proposed to regulate the protective activity of DJ-1. Uncoupling protein 4 (UCP4) is located in the inner membrane of mitochondria and functions to protect against oxidative stress. In this study, we used neuronal (SH-SY5Y) cells and DJ-1 knockout (KO) mice to elucidate whether DJ-1 regulated oxidative stress via modulating the expression of UCP4, and the underlying mechanism...
January 8, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29310909/oxa1-superfamily-new-members-found-in-the-er
#17
Yuanyuan Chen, Ross E Dalbey
Oxa1/Alb3/YidC family members promote the insertion of proteins into the mitochondrial inner membrane, the chloroplast thylakoid membrane, and the bacterial plasma membrane. Remarkably, two recent studies identify new Oxa1 homologs that reside in the endoplasmic reticulum (ER) and function in ER membrane protein biogenesis.
January 5, 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29305504/an-igaa-umob-family-protein-from-serratia-marcescens-regulates-motility-capsular-polysaccharide-and-secondary-metabolite-production
#18
Nicholas A Stella, Kimberly M Brothers, Jake D Callaghan, Angelina M Passerini, Cihad Sigindere, Preston J Hill, Xinyu Liu, Daniel J Wozniak, Robert M Q Shanks
Secondary metabolites are an important source of pharmaceuticals and key modulators of microbe-microbe interactions. The bacterium Serratia marcescens is part of the Enterobacteriaceae family of eubacteria and produces a number of biologically active secondary metabolites. In this study, we screened for novel regulators of secondary metabolites synthesized by a clinical isolate of S. marcescens and found mutations in a gene for an uncharacterized UmoB/IgaA family member here named gumB Mutation of gumB conferred a severe loss of secondary metabolites prodigiosin and serratamolide...
January 5, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29303598/endolymph-composition-paradigm-or-inevitability
#19
H Gagov, M Chichova, M Mladenov
This review is focused on the unusual composition of the endolymph of the inner ear and its function in mechanoelectrical transduction. The role of K(+) and Ca(2+) in excitatory influx, the very low Na(+), Ca(2+) and Mg(2+) concentrations of endolymph, stereocilia structure of hair cells and some proteins involved in mechanosensory signal transduction with emphasis on auditory receptors are presented and analyzed in more details. An alternative hypothetical model of ciliary structure and endolymph with a 'normal' composition is discussed...
January 5, 2018: Physiological Research
https://www.readbyqxmd.com/read/29301859/parl-partitions-the-lipid-transfer-protein-stard7-between-the-cytosol-and-mitochondria
#20
Shotaro Saita, Takashi Tatsuta, Philipp A Lampe, Tim König, Yohsuke Ohba, Thomas Langer
Intramembrane-cleaving peptidases of the rhomboid family regulate diverse cellular processes that are critical for development and cell survival. The function of the rhomboid protease PARL in the mitochondrial inner membrane has been linked to mitophagy and apoptosis, but other regulatory functions are likely to exist. Here, we identify the START domain-containing protein STARD7 as an intramitochondrial lipid transfer protein for phosphatidylcholine. We demonstrate that PARL-mediated cleavage during mitochondrial import partitions STARD7 to the cytosol and the mitochondrial intermembrane space...
January 4, 2018: EMBO Journal
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