1,266 research outputs found
The human SLC25A42 protein, ortholog of mitochondrial carrier Leu5p of S. cerevisiae, transports Coenzyme A and Adenosine 3’, 5’- diphosphate
No full textThe human SLC25A42 protein, ortholog of mitochondrial carrier Leu5p of S. cerevisiae, transports Coenzyme A and Adenosine 3’,5’-diphosphate
G. Fiermonte, E. Paradies, S. Todisco, C.M.T. Marobbio, M.A Di Noia, and F. Palmieri
Department of Pharmaco-Biology, Laboratory and Molecular Biology, University of Bari, Bari, Italy
The essential cofactor Coenzyme A (CoA) is required in many intra-mitochondrial metabolic pathways. The CoA is synthesized outside the mitochondrial matrix, therefore must be transported into mitochondria.
In S. cerevisiae, the mitochondrial carrier Leu5p is involved in the accumulation of CoA in the mitochondrial matrix. In fact, deletion of LEU5 (leu5) causes a reduction of mitochondrial coenzyme A (CoA) levels and growth defect on YP supplemented with glycerol or other non fermentative carbon sources.
The closest relatives of Leu5p in human are SLC25A16 (37% identity) and SLC25A42 (31% identity). In this study we provide direct evidence that SLC25A42 is a novel transporter of CoA.
SLC25A42 is localized in the mitochondrial inner membrane and is highly expressed in virtually all tissues. This protein was overexpressed in Escherichia coli, purified, reconstituted in phospholipid vesicles, and shown to transport CoA, dephospho-CoA, Adenosine 3’,5’-diphosphate (PAP), and (deoxy)adenine nucleotides with high specificity and by a counter-exchange mechanism.
The expression of SLC25A42 protein in LEU5 cells fully restores the phenotype of the LEU5 strain, indicating that the main function of both proteins is probably to catalyze the entry of CoA into mitochondria in exchange for adenine nucleotides and PAP
Metabolic Crossroad Between Macrophages and Cancer Cells:Overview of Hepatocellular Carcinoma
No full textThe metabolic interplay between macrophages and cancer cells mirrors the plasticity of both kinds of cells, which adapt to the microenvironment by sustaining cell growth and proliferation. In this way, cancer cells induce macrophage polarization, and, on the other hand, tumor-associated macrophages (TAMs) contribute to the survival of cancer cells. In a simplified manner, macrophages can assume two opposite subtypes: M1, pro-inflammatory and anti-tumor phenotype, and M2, anti-inflammatory and protumor phenotype. How do cancer cells induce macrophage polarization? Any actor involved in tumor growth, including the mitochondria, releases molecules into the tumor microenvironment (TME) that trigger a subtype transition. These metabolic changes are the primary cause of this polarization. Hepatocellular carcinoma (HCC), the prevalent type of liver primary tumor, is characterized by cells with extensive metabolic adaptions due to high flexibility in different environmental conditions. This review focuses on the main metabolic features of M1 and M2 macrophages and HCC cells underlying their metabolic behavior in response to TME
First person – Simona Amodeo
No full textABSTRACT
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Simona Amodeo is the first author on ‘Characterization of the novel mitochondrial genome replication factor MiRF172 in Trypanosoma brucei’, published in Journal of Cell Science. Simona is a PhD student in the lab of Torsten Ochsenreiter at the Institute of Cell Biology, University of Bern, Switzerland, investigating mitochondrial genome anchoring, replication and inheritance in Trypanosoma brucei.</jats:p
Identification of two human isoforms of the mitochondrial glutamate transporter: bacterial expression, functional characterization and tissue distribution
No full textIdentification of the mitochondrial glutamate transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms
No full textThe mitochondrial carriers are a family of transport proteins in the inner membranes of mitochondria. They shuttle substrates, metabolites, and cofactors through this membrane and connect cytoplasm functions with others in the matrix. Glutamate is co-transported with H(+) (or exchanged for OH(-)), but no protein has ever been associated with this activity. Two human expressed sequence tags encode proteins of 323 and 315 amino acids with 63% identity that are related to the aspartate-glutamate carrier, a member of the carrier family. They have been overexpressed in Escherichia coli and reconstituted into phospholipid vesicles. Their transport properties demonstrate that the two proteins are isoforms of the glutamate/H(+) symporter described in the past in whole mitochondria. Isoform 1 is expressed at higher levels than isoform 2 in all the tissues except in brain, where the two isoforms are expressed at comparable levels. The differences in expression levels and kinetic parameters of the two isoforms suggest that isoform 2 matches the basic requirement of all tissues especially with respect to amino acid degradation, and isoform 1 becomes operative to accommodate higher demands associated with specific metabolic functions such as ureogenesis
New Insights into NF-κB Signaling in Innate Immunity: Focus on Immunometabolic Crosstalks
No full textThe nuclear factor kappa B (NF-κB) is a family of transcription factors that, beyond their numberless functions in various cell processes, play a pivotal role in regulating immune cell activation. Two main pathways—canonical and non-canonical—are responsible for NF-κB activation and heterodimer translocation into the nucleus. A complex crosstalk between NF-κB signaling and metabolism is emerging in innate immunity. Metabolic enzymes and metabolites regulate NF-κB activity in many cases through post-translational modifications such as acetylation and phosphorylation. On the other hand, NF-κB affects immunometabolic pathways, including the citrate pathway, thereby building an intricate network. In this review, the emerging findings about NF-κB function in innate immunity and the interplay between NF-κB and immunometabolism have been discussed. These outcomes allow for a deeper comprehension of the molecular mechanisms underlying NF-κB function in innate immune cells. Moreover, the new insights are important in order to perceive NF-κB signaling as a potential therapeutic target for inflammatory/immune chronic diseases
Materiali e discussioni per l'analisi dei testi classici. Indici 1-60
No full textIl volume raccoglie e riassume tutti gli articoli apparsi nei volumi 1-60 della rivista «Materiali e discussioni per l’analisi dei testi classici» («MD»), nel periodo compreso tra il 1978 e il 2008. Esso è diviso in tre parti. Nella prima sono riportati in successione i singoli numeri della rivista, con il relativo sommario. Nella seconda compaiono gli articoli riuniti in sequenza cronologica, sotto il nome dell’Autore e ognuno con un proprio numero d’ordine: di ogni articolo è fornito il sunto, con i concetti, le argomentazioni salienti, i principali luoghi discussi. Nella terza parte sono elencati gli Autori antichi e i Nomi e parole notevoli, con il rinvio al numero d’ordine dell’articolo. Le schedature dei numeri 1-30 sono curate da Andrea Cucchiarelli, quelle dei numeri 31-60 da Simona Fortini.The volume collects and summarizes all the articles published in Volumes 1-60 of the journal "Materiali e discussioni per l’analisi dei testi classici” ("MD"), in the period between 1978 and 2008. It is divided into three parts. In the first part the individual issues of the journal are summarized with the table of contents. In the second part the articles appear in chronological order, under the name of the author and each with its own serial number: each item is provided with a summary including the main points of argumentation and the loci discussed. The third part contains the indexes of the ancient authors, of the names and of the most relevant things and words, with reference to the number of the item. The profiling of the numbers 1-30 is cared for by Andrea Cucchiarelli, those of the numbers 31-60 by Simona Fortini
Boccaccio nel Seicento: censure e recuperi della "compassione"
No full textSIMONA MORANDO, Boccaccio in the sixteenth century: censorship and recovery ofthe «compassion»
In the introduction of this paper, the literature of the seventeenth century is defined as a writing of compassion but not of consolation (quotations from Giovanni Cisano, Torquato Accetto, Emanuele Tesauro, G. B. Marino). The distance between the
writers studied here and Boccaccio is due to the censored editions of the Decameron in sixteenth century, to the censorship of Boccaccio as a «maestro d’amore», to his unrefined language, to his interpretation by many critics as a light and burlesque author. But, as reported in a writing by Boccalini, Boccaccio’s Latin works are very much appreciated in seventeenth century literature. This is especially the case of De casibus virorum illustrium, a gloomy and pessimistic book about misfortunes of famous men and about compassion, which nevertheless believes in the ability of letters to give back fame to ruined men. As shown in the conclusion
through some writings by Tassoni, many other seventeenth century authors do not have this kind of hope
The Human SLC25A33 and SLC25A36 are two Mitochondrial Pyrimidine Nucleotide Transporters
No full textThe human SLC25A33 and SLC25A36 are two members of solute carrier family 25 (SLC25) that transports a variety of metabolites across the inner mitochondrial membrane, connecting cytosolic and matrix functions. These two proteins are the close relatives of the Saccharomyces cerevisiae Rim2p, the mitochondrial carrier for pyrimidine nucleotides (1), whose absence by deletion of RIM2 gene causes total loss of mtDNA and lack of growth on non-fermentative carbon sources (2). This study reports the identification and in-depth functional characterization of SLC25A33 and of SLC25A36. The SLC25A33 and SLC25A36 genes were overexpressed in Escherichia coli and the recombinant proteins were purified and reconstituted in liposomes. Recombinant SLC25A33 transports uracil, thymine, and cytosine (deoxy)-nucleoside di- and tri-phosphates by an antiport mechanism and SLC25A36 transports cytosine and uracil (deoxy)nucleoside mono-, di-, and triphosphates by uniport and antiport. Furthermore, subcellular localization demonstrated that SLC25A36 is a mitochondrial protein as previously shown for SLC25A33 (3). These results indicate that SLC25A33 and SLC25A36 are mitochondrial transporters for pyrimidine ribo- and deoxynucleotides. These nucleotides are essential for the synthesis of DNA and the various types of RNA including the RNA primers necessary for the initiation of DNA replication and repair, as well as the products of their breakdown. Furthermore, in vivo, the expression of SLC25A33 or SLC25A36 in RIM2 haploid strains restores the phenotype of S. cerevisiae by rescuing mtDNA, mitochondrial respiration, mitochondrial membrane potential and growth on glycerol and other respiratory substrates. These findings strongly support SLC25A33 and SLC25A36 controlling the uptake of pyrimidine (deoxy)nucleotides into mitochondria
Identification of other two mitochondrial carriers in Saccharomyces cerevisiae: the transporters for pyrimidine nucleotides and for NAD+
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