Fucosylated ubiquitin and orthogonally glycosylated mutant A28C: conceptually new ligands for lectin (BambL).

Two orthogonal, metal free click reactions, enabled to glycosylate ubiquitin and its mutant A28C forming two protein scaffolds with high affinity for BambL, a lectin from the human pathogen . A new fucoside analogue, with high affinity with BambL, firstly synthetized and co-crystallized with the protein target, provided the insights for sugar determinants grafting onto ubiquitin. Three ubiquitin-based glycosides were thus assembled.

Protein Glycosylation through Sulfur Fluoride Exchange (SuFEx) Chemistry: The Key Role of a Fluorosulfate Thiolactoside.

Protein glycosylation is the most complex post-translational modification process. More than 50 % of human cells proteins are glycosylated, whereas bacteria such as E. coli do not have this modification machinery.

Relation Between Mitochondrial Membrane Potential and ROS Formation.

Mitochondria are considered the main source of reactive oxygen species (ROS) in the cell. For this reason they have been recognized as a source of various pathological conditions as well as aging. Chronic increase in the rate of ROS production is responsible for the accumulation of ROS-associated damages in DNA, proteins, and lipids and may result in progressive cell dysfunctions and, in a consequence, apoptosis, increasing the overall probability of an organism's pathological conditions.

Mechanistic Role of mPTP in Ischemia-Reperfusion Injury.

Acute myocardial infarction (MI) is a major cause of death and disability worldwide. The treatment of choice for reducing ischemic injury and limiting infarct size (IS) in patients with ST-segment elevation MI (STEMI) is timely and effective myocardial reperfusion via primary percutaneous coronary intervention (PCI). However, myocardial reperfusion itself may induce further cardiomyocyte death, a phenomenon known as reperfusion injury (RI).

The purinergic receptor subtype P2Y2 mediates chemotaxis of neutrophils and fibroblasts in fibrotic lung disease.

Idiopathic pulmonary fibrosis (IPF) is a devastating disease with few available treatment options. Recently, the involvement of purinergic receptor subtypes in the pathogenesis of different lung diseases has been demonstrated. Here we investigated the role of the purinergic receptor subtype P2Y2 in the context of fibrotic lung diseases.

SuFEx: a metal-free click ligation for multivalent biomolecules.

The Sulfur(vi) Fluoride Exchange (SuFEx), revived by Sharpless and co-workers from an unrecognized state, is an emerging new click reaction that is based on the high reactivity of sulfonyl fluorides and fluorosulfates with suitable nucleophiles such as silyl ethers and amines. Hence, we comment in this Perspective on the use of SuFEx for the synthesis of a new family of sugar containing sulfonamides from the reaction of a glycosylsulfonyl fluoride with aliphatic amines. We also highlight the applications of SuFEx to multivalent scaffolds such as tetraamino- and tetrafluorosulfonyl-calixarene leading to sulfonamide-linked sugar and iminosugar clusters.

Validating the alkene and alkyne hydrophosphonylation as an entry to organophosphonates.

The first paper on the hydrophosphonylation of terminal alkenes was published in 1958 by Stiles and coworkers. Afterwards various papers described organometal-catalyzed and free-radical reactions leading to linear anti-Markovnikov adducts and/or branched Markovnikov products. In 1996 Han and Tanaka reported the first example of alkyne hydrophosphonylation catalyzed by a palladium complex.

A family with paroxysmal nonkinesigenic dyskinesias (PNKD): evidence of mitochondrial dysfunction.

Introduction: Paroxysmal nonkinesigenic dyskinesia (PNKD) is a rare movement disorder characterized by sudden attacks of involuntary movements. Familial PNKD is an autosomal dominant trait, caused by mutations in the myofibrillogenesis regulator 1 (MR-1) gene on chromosome 2q35. Three different mutations have been described; all of them reside in the N-terminal region common to isoforms L and S, that has been suggested to code for a mitochondrial targeting sequence, necessary for the correct sub-cellular localization of the protein into mitochondria.

The mitochondrial permeability transition pore is a dispensable element for mitochondrial calcium efflux.

The mitochondrial permeability transition pore (mPTP) has long been known to have a role in mitochondrial calcium (Ca(2+)) homeostasis under pathological conditions as a mediator of the mitochondrial permeability transition and the activation of the consequent cell death mechanism. However, its role in the context of mitochondrial Ca(2+) homeostasis is not yet clear. Several studies that were based on PPIF inhibition or knock out suggested that mPTP is involved in the Ca(2+) efflux mechanism, while other observations have revealed the opposite result.

Tumor necrosis factor-α impairs oligodendroglial differentiation through a mitochondria-dependent process.

Mitochondrial defects, affecting parameters such as mitochondrial number and shape, levels of respiratory chain complex components and markers of oxidative stress, have been associated with the appearance and progression of multiple sclerosis. Nevertheless, mitochondrial physiology has never been monitored during oligodendrocyte progenitor cell (OPC) differentiation, especially in OPCs challenged with proinflammatory cytokines. Here, we show that tumor necrosis factor alpha (TNF-α) inhibits OPC differentiation, accompanied by altered mitochondrial calcium uptake, mitochondrial membrane potential, and respiratory complex I activity as well as increased reactive oxygen species production.

ATP/P2X7 axis modulates myeloid-derived suppressor cell functions in neuroblastoma microenvironment.

Tumor microenvironment of solid tumors is characterized by a strikingly high concentration of adenosine and ATP. Physiological significance of this biochemical feature is unknown, but it has been suggested that it may affect infiltrating immune cell responses and tumor progression. There is increasing awareness that many of the effects of extracellular ATP on tumor and inflammatory cells are mediated by the P2X7 receptor (P2X7R).

Isolation of plasma membrane-associated membranes from rat liver.

Dynamic interplay between intracellular organelles requires a particular functional apposition of membrane structures. The organelles involved come into close contact, but do not fuse, thereby giving rise to notable microdomains; these microdomains allow rapid communication between the organelles. Plasma membrane-associated membranes (PAMs), which are microdomains of the plasma membrane (PM) interacting with the endoplasmic reticulum (ER) and mitochondria, are dynamic structures that mediate transport of proteins, lipids, ions and metabolites.

Transglutaminase 2 contributes to apoptosis induction in Jurkat T cells by modulating Ca2+ homeostasis via cross-linking RAP1GDS1.

Background: Transglutaminase 2 (TG2) is a protein cross-linking enzyme known to be associated with the in vivo apoptosis program of T cells. However, its role in the T cell apoptosis program was not investigated yet.

Results: Here we report that timed overexpression of both the wild type (wt) and the cross-linking mutant of TG2 induced apoptosis in Jurkat T cells, the wt being more effective.

The endoplasmic reticulum-mitochondria connection: one touch, multiple functions.

The endoplasmic reticulum (ER) and mitochondria are tubular organelles with a characteristic "network structure" that facilitates the formation of interorganellar connections. The ER and mitochondria join together at multiple contact sites to form specific domains, termed mitochondria-ER associated membranes (MAMs), with distinct biochemical properties and a characteristic set of proteins. The functions of these two organelles are coordinated and executed at the ER-mitochondria interface, which provides a platform for the regulation of different processes.

Perturbed mitochondrial Ca2+ signals as causes or consequences of mitophagy induction.

Mitophagy is an essential process that maintains mitochondrial quality and number, thus limiting cellular degeneration. Along with apoptosis, mitophagy participates in cellular fate decisions by eliminating damaged mitochondria. A variety of mitochondrial parameters, such as structure, membrane potential, and reactive oxygen species, are key determinants in triggering the mitophagic machinery.

Subcellular calcium measurements in mammalian cells using jellyfish photoprotein aequorin-based probes.

The jellyfish Aequorea victoria produces a 22-kDa protein named aequorin that has had an important role in the study of calcium (Ca(2+)) signaling. Aequorin reacts with Ca(2+) via oxidation of the prosthetic group, coelenterazine, which results in emission of light. This signal can be detected by using a special luminescence reader (called aequorinometer) or luminescence plate readers.

Chemoresistance and Cancer-Related Inflammation: Two Hallmarks of Cancer Connected by an Atypical Link, PKCζ.

Atypical protein kinase C isoforms are serine threonine kinases involved in various pathological conditions. In recent years, the PKCζ isoform has emerged as an important regulator of multiple cellular processes operating in cancer. In this review, we will focus on the PKCζ isoform as an oxidative-sensing kinase involved in cancer-related inflammation and chemoresistance.

A(1) and A(3) adenosine receptors inhibit LPS-induced hypoxia-inducible factor-1 accumulation in murine astrocytes.

Adenosine (Ado) exerts neuroprotective and anti-inflammatory functions by acting through four receptor subtypes A1, A2A, A2B and A3. Astrocytes are one of its targets in the central nervous system. Hypoxia-inducible factor-1 (HIF-1), a master regulator of oxygen homeostasis, is induced after hypoxia, ischemia and inflammation and plays an important role in brain injury.

Identification of PTEN at the ER and MAMs and its regulation of Ca(2+) signaling and apoptosis in a protein phosphatase-dependent manner.

The tumor suppressor activity of PTEN (phosphatase and tensin homolog deleted on chromosome 10) is thought to be largely attributable to its lipid phosphatase activity. PTEN dephosphorylates the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate to directly antagonize the phosphoinositide 3-kinase-Akt pathway and prevent the activating phosphorylation of Akt. PTEN has also other proposed mechanisms of action, including a poorly characterized protein phosphatase activity, protein-protein interactions, as well as emerging functions in different compartment of the cells such as nucleus and mitochondria.

PRKCB/protein kinase C, beta and the mitochondrial axis as key regulators of autophagy.

Autophagy is the major intracellular system of degradation, and it plays an essential role in various biological events. Recent observations indicate that autophagy is modulated in response to the energy status of the mitochondrial compartment. However, the exact signaling mechanism that controls autophagy under these conditions remains unclear.

H-Ras-driven tumoral maintenance is sustained through caveolin-1-dependent alterations in calcium signaling.

A growing body of research has highlighted the complex range of tumoral traits acquired during H-Ras-driven transformation and maintenance, which include proliferative signaling, growth suppressor evasion and resistance to cell death. Clear molecular information about these processes is not yet available, but recent evidence has provided solid support for the importance of mitochondria. Here, we show that the induction of oncogenic H-Ras leads to changes in intracellular calcium (Ca(2+)), evaluate the temporal relationship between oncogene expression and mitochondrial physiology, and demonstrate that Ca(2+) homeostasis is altered by caveolin-1, a protein that has a key role in tumor maintenance.

Mitochondrial calcium uniporter, MiRNA and cancer: Live and let die.

Mitochondria receive calcium (Ca(2+)) signals from endoplasmic reticulum (ER) and decode them into pro-apoptotic inputs, which lead to cell death. Therefore, mitochondrial Ca(2+) overload is considered a fundamental trigger of the apoptotic process, and several oncogenes and tumor suppressors modify the activity of protein involved in Ca(2+) homeostasis to control apoptosis. The identification of the channel responsible for mitochondrial Ca(2+) entry, the Mitochondrial Ca(2+)Uniporter (MCU), together with its regulatory components, MICU1 and MCUR1, provides new molecular tools to investigate this process.