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Jonathan R Friedman, Muthukumar Kannan, Alexandre Toulmay, Calvin H Jan, Jonathan S Weissman, William A Prinz, Jodi Nunnari
Spatial organization of phospholipid synthesis in eukaryotes is critical for cellular homeostasis. The synthesis of phosphatidylcholine (PC), the most abundant cellular phospholipid, occurs redundantly via the ER-localized Kennedy pathway and a pathway that traverses the ER and mitochondria via membrane contact sites. The basis of the ER-mitochondrial PC synthesis pathway is the exclusive mitochondrial localization of a key pathway enzyme, phosphatidylserine decarboxylase Psd1, which generates phosphatidylethanolamine (PE)...
December 26, 2017: Developmental Cell
Non Miyata, Naoto Goda, Keiji Matsuo, Takeshi Hoketsu, Osamu Kuge
Cardiolipin (CL) is synthesized from phosphatidic acid (PA) through a series of enzymatic reactions occurring at the mitochondrial inner membrane (MIM). Ups1-Mdm35 mediates PA transfer from the mitochondrial outer membrane (MOM) to the MIM in the yeast Saccharomyces cerevisiae. Deletion of UPS1 leads to a ~80% decrease in the cellular CL level. However, the CL accumulation in ups1∆ cells is enhanced by the depletion of Ups2, which forms a protein complex with Mdm35 and mediates phosphatidylserine (PS) transfer from the MOM to the MIM for phosphatidylethanolamine (PE) synthesis by a PS decarboxylase, Psd1...
November 27, 2017: Scientific Reports
Ariane Wagner, Francesca Di Bartolomeo, Isabella Klein, Claudia Hrastnik, Kim Nguyen Doan, Thomas Becker, Günther Daum
Phosphatidylserine decarboxylase 1 (Psd1p) catalyzes the formation of the majority of phosphatidylethanolamine (PE) in the yeast Saccharomyces cerevisiae. Psd1p is localized to mitochondria, anchored to the inner mitochondrial membrane (IMM) through membrane spanning domains and oriented towards the mitochondrial intermembrane space. We found that Psd1p harbors at least two inner membrane-associated domains, which we named IM1 and IM2. IM1 is important for proper orientation of Psd1p within the IMM (Horvath et al...
February 2018: Biochimica et Biophysica Acta
Sónia Gonçalves, Patrícia M Silva, Mário R Felício, Luciano N de Medeiros, Eleonora Kurtenbach, Nuno C Santos
Candida albicans is an important human pathogen, causing opportunistic infections. The adhesion of planktonic cells to a substrate is the first step for biofilm development. The antimicrobial peptide (AMP) Psd1 is a defensin isolated from Pisum sativum seeds. We tested the effects of this AMP on C. albicans biofilms and planktonic cells, comparing its activity with amphotericin B and fluconazole. Three C. albicans variants were studied, one of them a mutant deficient in glucosylceramide synthase, conferring resistance to Psd1 antifungal action...
2017: Frontiers in Cellular and Infection Microbiology
D A Gonzalez, T Jia, J H Pinzón, S F Acevedo, S A Ojelade, B Xu, N Tay, S Desrivières, J L Hernandez, T Banaschewski, C Büchel, A L W Bokde, P J Conrod, H Flor, V Frouin, J Gallinat, H Garavan, P A Gowland, A Heinz, B Ittermann, M Lathrop, J-L Martinot, T Paus, M N Smolka, A R Rodan, G Schumann, A Rothenfluh
Ubiquitously expressed genes have been implicated in a variety of specific behaviors, including responses to ethanol. However, the mechanisms that confer this behavioral specificity have remained elusive. Previously, we showed that the ubiquitously expressed small GTPase Arf6 is required for normal ethanol-induced sedation in adult Drosophila. Here, we show that this behavioral response also requires Efa6, one of (at least) three Drosophila Arf6 guanine exchange factors. Ethanol-naive Arf6 and Efa6 mutants were sensitive to ethanol-induced sedation and lacked rapid tolerance upon re-exposure to ethanol, when compared with wild-type flies...
June 13, 2017: Molecular Psychiatry
Oluwaseun B Ogunbona, Ouma Onguka, Elizabeth Calzada, Steven M Claypool
Phosphatidylserine decarboxylase 1 (Psd1p), an ancient enzyme that converts phosphatidylserine to phosphatidylethanolamine in the inner mitochondrial membrane, must undergo an autocatalytic self-processing event to gain activity. Autocatalysis severs the protein into a large membrane-anchored β subunit that noncovalently associates with the small α subunit on the intermembrane space side of the inner membrane. Here, we determined that a temperature sensitive (ts) PSD1 allele is autocatalytically impaired and that its fidelity is closely monitored throughout its life cycle by multiple mitochondrial quality control proteases...
September 1, 2017: Molecular and Cellular Biology
Kyung-Lim Joa, Sohee Moon, Ji-Hye Kim, Dong Wun Shin, Kyoung-Hee Lee, Seon Jung, Myeong-Ok Kim, Chang-Hwan Kim, Han-Young Jung, Ju-Hee Kang
Although stroke elicits progressive cognitive decline and is a leading cause of dementia, molecular interplay between stroke and Alzheimer's disease (AD) pathology has not been fully elucidated. Furthermore, studies on the effects of post-stroke rehabilitation on AD pathology are limited. We evaluated the acute effect of stroke on tau modification, and the molecular effects of task-specific training (TST) on tau modification using a model of photochemically-induced thrombosis (PIT)-induced cortical infarction...
September 2017: Neurochemistry International
Adam Kawałek, Chandhuru Jagadeesan, Ida J van der Klei
The non-bilayer forming lipids cardiolipin (CL) and phosphatidylethanolamine (PE) modulate membrane curvature, facilitate membrane fusion and affect the stability and function of membrane proteins. Yeast peroxisomal membranes contain significant amounts of CL and PE. We analysed the effect of CL deficiency and PE depletion on peroxisome biogenesis and proliferation in Saccharomyces cerevisiae. Our data indicate that deletion of CRD1, which encodes cardiolipin synthase, does not affect peroxisome biogenesis or abundance, both at peroxisome repressing (glucose) or inducing (oleate) growth conditions...
November 11, 2016: Biochemical and Biophysical Research Communications
Shaoxiao Wang, Siyuan Zhang, Chuan Xu, Addie Barron, Floyd Galiano, Dhaval Patel, Yong Joo Lee, Guy A Caldwell, Kim A Caldwell, Stephan N Witt
We have been investigating the role that phosphatidylethanolamine (PE) and phosphatidylcholine (PC) content plays in modulating the solubility of the Parkinson's disease protein alpha-synuclein (α-syn) using Saccharomyces cerevisiae and Caenorhabditis elegans. One enzyme that synthesizes PE is the conserved enzyme phosphatidylserine decarboxylase (Psd1/yeast; PSD-1/worms), which is lodged in the inner mitochondrial membrane. We previously found that decreasing the level of PE due to knockdown of Psd1/psd-1 affects the homeostasis of α-syn in vivo...
2016: PloS One
Francesca Di Bartolomeo, Ariane Wagner, Günther Daum
Phosphatidylethanolamine is one of the most abundant phospholipids whose major amounts are formed by phosphatidylserine decarboxylases (PSD). Here we provide a comprehensive description of different types of PSDs in the different kingdoms of life. In eukaryotes, type I PSDs are mitochondrial enzymes, whereas other PSDs are localized to other cellular compartments. We describe the role of mitochondrial Psd1 proteins, their function, enzymology, biogenesis, assembly into mitochondria and their contribution to phospholipid homeostasis in much detail...
January 2017: Biochimica et Biophysica Acta
Antoni W James, Ramachandran Gowsalya, Vasanthi Nachiappan
The endoplasmic reticulum (ER) has numerous biological functions including protein synthesis, protein folding, and lipid synthesis. The CAX4 gene encodes dolichyl pyrophosphate (Dol-PP) phosphatase, which is involved in protein N-glycosylation. In cax4Δ cells, the N-glycosylation of the vacuolar carboxypeptidase (CPY) was severely affected, and expression of the ER chaperone Kar2p was elevated, which resulted in UPR activation as an adaptive response. The cax4Δ cell growth was reduced, and this could be attributed to the formation of clumped aggregates, high vesiculation of the intracellular membrane, and plasma membrane alterations were depicted using DiOC6 fluorescence...
November 2016: Biochimica et Biophysica Acta
C M Fernandes, P A de Castro, A Singh, F L Fonseca, M D Pereira, T V M Vila, G C Atella, S Rozental, M Savoldi, M Del Poeta, G H Goldman, E Kurtenbach
C8-desaturated and C9-methylated glucosylceramide (GlcCer) is a fungal-specific sphingolipid that plays an important role in the growth and virulence of many species. In this work, we investigated the contribution of Aspergillus nidulans sphingolipid Δ8-desaturase (SdeA), sphingolipid C9-methyltransferases (SmtA/SmtB) and glucosylceramide synthase (GcsA) to fungal phenotypes, sensitivity to Psd1 defensin and Galleria mellonella virulence. We showed that ΔsdeA accumulated C8-saturated and unmethylated GlcCer, while gcsA deletion impaired GlcCer synthesis...
November 2016: Molecular Microbiology
Mari J Aaltonen, Jonathan R Friedman, Christof Osman, Bénédicte Salin, Jean-Paul di Rago, Jodi Nunnari, Thomas Langer, Takashi Tatsuta
Mitochondria exert critical functions in cellular lipid metabolism and promote the synthesis of major constituents of cellular membranes, such as phosphatidylethanolamine (PE) and phosphatidylcholine. Here, we demonstrate that the phosphatidylserine decarboxylase Psd1, located in the inner mitochondrial membrane, promotes mitochondrial PE synthesis via two pathways. First, Ups2-Mdm35 complexes (SLMO2-TRIAP1 in humans) serve as phosphatidylserine (PS)-specific lipid transfer proteins in the mitochondrial intermembrane space, allowing formation of PE by Psd1 in the inner membrane...
June 6, 2016: Journal of Cell Biology
Fang Ji, Min Xu, Chao Wang, Xiaoyuan Li, Wei Gao, Yunfei Zhang, Baorui Wang, Guangping Tang, Xiaobin Yue
The cubic Fe3O4 nanoparticles with sharp horns that display the size distribution between 100 and 200 nm are utilized to substitute the magnetic sensitive medium (carbonyl iron powders, CIPs) and abrasives (CeO2/diamond) simultaneously which are widely employed in conventional magnetorheological finishing fluid. The removal rate of this novel fluid is extremely low compared with the value of conventional one even though the spot of the former is much bigger. This surprising phenomenon is generated due to the small size and low saturation magnetization (M s) of Fe3O4 and corresponding weak shear stress under external magnetic field according to material removal rate model of magnetorheological finishing (MRF)...
December 2016: Nanoscale Research Letters
Stephan N Witt
We recently reported that knocking down the enzyme phosphatidylserine decarboxylase, which synthesizes the phospholipid phosphatidylethanolamine (PE) in mitochondria, perturbs the homeostasis of the human Parkinson disease (PD) protein α-synuclein (expressed in yeast or worms). In yeast, low PE in the psd1Δ deletion mutant induces α-synuclein to enter cytoplasmic foci, the level of this protein increases 3-fold compared to wild-type cells, and the mutant cells are severely sick. The metabolite ethanolamine protects both yeast and worms from the deleterious synergistic effects of low mitochondrial PE and α-synuclein...
December 2014: Communicative & Integrative Biology
Non Miyata, Takuya Miyoshi, Takanori Yamaguchi, Toshimitsu Nakazono, Motohiro Tani, Osamu Kuge
Phosphatidylethanolamine (PE) in the yeast Saccharomyces cerevisiae is synthesized through decarboxylation of phosphatidylserine (PS), catalysed by PS decarboxylase 1 (Psd1p) and 2 (Psd2p) and the cytidine 5'-diphosphate (CDP)-ethanolamine (CDP-Etn) pathway. PSD1 null (psd1Δ) and PSD2 null (psd2Δ) mutants are viable in a synthetic minimal medium, but a psd1Δ psd2Δ double mutant exhibits Etn auxotrophy, which is incorporated into PE through the CDP-Etn pathway. We have previously shown that psd1Δ is synthetic lethal with deletion of VID22 (vid22Δ) [Kuroda et al...
December 15, 2015: Biochemical Journal
Martina Gsell, Ariane Fankl, Lisa Klug, Gerald Mascher, Claudia Schmidt, Claudia Hrastnik, Günther Zellnig, Günther Daum
In a previous study we demonstrated up-regulation of the yeast GPH1 gene under conditions of phosphatidylethanolamine (PE) depletion caused by deletion of the mitochondrial (M) phosphatidylserine decarboxylase 1 (PSD1) (Gsell et al., 2013, PLoS One. 8(10):e77380. doi: 10.1371/journal.pone.0077380). Gph1p has originally been identified as a glycogen phosphorylase catalyzing degradation of glycogen to glucose in the stationary growth phase of the yeast. Here we show that deletion of this gene also causes decreased levels of phosphatidylcholine (PC), triacylglycerols and steryl esters...
2015: PloS One
Julie M Wolf, Javier Espadas, Jose Luque-Garcia, Todd Reynolds, Arturo Casadevall
Microbial secretion is integral for regulating cell homeostasis as well as releasing virulence factors during infection. The genes encoding phosphatidylserine synthase (CHO1) and phosphatidylserine decarboxylase (PSD1 and PSD2) are Candida albicans genes involved in phospholipid biosynthesis, and mutations in these genes affect mitochondrial function, cell wall thickness, and virulence in mice. We tested the roles of these genes in several agar-based secretion assays and observed that the cho1Δ/Δ and psd1Δ/Δ psd2Δ/Δ strains manifested less protease and phospholipase activity...
August 2015: Eukaryotic Cell
Juan Du, Hien T T Ngo, KyungHwa Won, Ki-Young Kim, Feng-Xie Jin, Tae-Hoo Yi
Strain THG-EP9T, a Gram-stain-negative, aerobic, motile, rod-shaped bacterium was isolated from field-grown eggplant (Solanum melongena) rhizosphere soil collected in Pyeongtaek, Gyeonggi-do, Republic of Korea. Based on 16S rRNA gene sequence comparisons, strain THG-EP9T had closest similarity with Chryseobacterium ginsenosidimutans THG 15T (97.3 % 16S rRNA gene sequence similarity), Chryseobacterium soldanellicola PSD1-4T (97.2%), Chryseobacterium zeae JM-1085T (97.2%) and Chryseobacterium indoltheticum LMG 4025T (96...
August 2015: International Journal of Systematic and Evolutionary Microbiology
P Rockenfeller, M Koska, F Pietrocola, N Minois, O Knittelfelder, V Sica, J Franz, D Carmona-Gutierrez, G Kroemer, F Madeo
Autophagy is a cellular recycling program that retards ageing by efficiently eliminating damaged and potentially harmful organelles and intracellular protein aggregates. Here, we show that the abundance of phosphatidylethanolamine (PE) positively regulates autophagy. Reduction of intracellular PE levels by knocking out either of the two yeast phosphatidylserine decarboxylases (PSD) accelerated chronological ageing-associated production of reactive oxygen species and death. Conversely, the artificial increase of intracellular PE levels, by provision of its precursor ethanolamine or by overexpression of the PE-generating enzyme Psd1, significantly increased autophagic flux, both in yeast and in mammalian cell culture...
March 2015: Cell Death and Differentiation
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