Spatially organised mitochondrial calcium uptake through a novel pathway in chick neurones.
AuthorsCoatesworth W, Bolsover S
JournalCell Calcium
PubMed ID16338004
'A brief depolarisation of chick sensory neurones evokes a calcium increase in mitochondria that peaks 1-2s after the depolarisation event and then decays over tens of seconds. Peripheral mitochondria take up more calcium than do central ones, even when the cytosolic calcium increase is spatially homogeneous. The calcium influx into ... More
Differential activity-dependent regulation of the lateral mobilities of AMPA and NMDA receptors.
AuthorsGroc L, Heine M, Cognet L, Brickley K, Stephenson FA, Lounis B, Choquet D
JournalNat Neurosci
PubMed ID15208630
'The basis for differences in activity-dependent trafficking of AMPA receptors (AMPARs) and NMDA receptors (NMDARs) remains unclear. Using single-molecule tracking, we found different lateral mobilities for AMPARs and NMDARs: changes in neuronal activity modified AMPAR but not NMDAR mobility, whereas protein kinase C activation modified both. Differences in mobility were ... More
NMDA receptor surface mobility depends on NR2A-2B subunits.
AuthorsGroc L, Heine M, Cousins SL, Stephenson FA, Lounis B, Cognet L, Choquet D
JournalProc Natl Acad Sci U S A
PubMed ID17124177
'The NR2 subunit composition of NMDA receptors (NMDARs) varies during development, and this change is important in NMDAR-dependent signaling. In particular, synaptic NMDAR switch from containing mostly NR2B subunit to a mixture of NR2B and NR2A subunits. The pathways by which neurons differentially traffic NR2A- and NR2B-containing NMDARs are poorly ... More
Subcellular localization of Nox4 and regulation in diabetes.
AuthorsBlock K, Gorin Y, Abboud HE,
JournalProc Natl Acad Sci U S A
PubMed ID19706525
'Oxidative stress is implicated in human diseases. Some of the oxidative pathways are harbored in the mitochondria. NAD(P)H oxidases have been identified not only in phagocytic but also in somatic cells. Nox4 is the most ubiquitous of these oxidases and is a major source of reactive oxygen species (ROS) in ... More
Long-term exposure to CdTe quantum dots causes functional impairments in live cells.
AuthorsCho SJ, Maysinger D, Jain M, Röder B, Hackbarth S, Winnik FM
JournalLangmuir
PubMed ID17279683
'Several studies suggested that the cytotoxic effects of quantum dots (QDs) may be mediated by cadmium ions (Cd2+) released from the QDs cores. The objective of this work was to assess the intracellular Cd2+ concentration in human breast cancer MCF-7 cells treated with cadmium telluride (CdTe) and core/shell cadmium selenide/zinc ... More
Ketamine induces toxicity in human neurons differentiated from embryonic stem cells via mitochondrial apoptosis pathway.
AuthorsBosnjak ZJ, Yan Y, Canfield S, Muravyeva MY, Kikuchi C, Wells CW, Corbett JA, Bai X,
JournalCurr Drug Saf
PubMed ID22873495
'Ketamine is widely used for anesthesia in pediatric patients. Growing evidence indicates that ketamine causes neurotoxicity in a variety of developing animal models. Our understanding of anesthesia neurotoxicity in humans is currently limited by difficulties in obtaining neurons and performing developmental toxicity studies in fetal and pediatric populations. It may ... More
A role for mitochondria in NLRP3 inflammasome activation.
AuthorsZhou R, Yazdi AS, Menu P, Tschopp J,
JournalNature
PubMed ID21124315
'An inflammatory response initiated by the NLRP3 inflammasome is triggered by a variety of situations of host ''danger'', including infection and metabolic dysregulation. Previous studies suggested that NLRP3 inflammasome activity is negatively regulated by autophagy and positively regulated by reactive oxygen species (ROS) derived from an uncharacterized organelle. Here we ... More
Selective fluorescent imaging of superoxide in vivo using ethidium-based probes.
AuthorsRobinson KM, Janes MS, Pehar M, Monette JS, Ross MF, Hagen TM, Murphy MP, Beckman JS
JournalProc Natl Acad Sci U S A
PubMed ID17015830
'The putative oxidation of hydroethidine (HE) has become a widely used fluorescent assay for the detection of superoxide in cultured cells. By covalently joining HE to a hexyl triphenylphosphonium cation (Mito-HE), the HE moiety can be targeted to mitochondria. However, the specificity of HE and Mito-HE for superoxide in vivo ... More
Visualizing formation and dynamics of vacuoles in living cells using contrasting dextran-bound indicator: endocytic and nonendocytic vacuoles.
'Here we describe a technique that allows us to visualize in real time the formation and dynamics (fusion, changes of shape, and translocation) of vacuoles in living cells. The technique involves infusion of a dextran-bound fluorescent probe into the cytosol of the cell via a patch pipette, using the whole-cell ... More
Therapeutic efficacy of FTY720 in a rat model of NK-cell leukemia.
AuthorsLiao A, Broeg K, Fox T, Tan SF, Watters R, Shah MV, Zhang LQ, Li Y, Ryland L, Yang J, Aliaga C, Dewey A, Rogers A, Loughran K, Hirsch L, Jarbadan NR, Baab KT, Liao J, Wang HG, Kester M, Desai D, Amin S, Loughran TP, Liu X,
JournalBlood
PubMed ID21768294
'NK-cell leukemia is a clonal expansion of NK cells. The illness can occur in an aggressive or chronic form. We studied cell lines from human and rat NK-cell leukemias (aggressive NK-cell leukemia) as well as samples from patients with chronic NK-cell leukemia to investigate pathogenic mechanisms. Here we report that ... More
Essential requirement for sphingosine kinase 2 in a sphingolipid apoptosis pathway activated by FTY720 analogues.
AuthorsDon AS, Martinez-Lamenca C, Webb WR, Proia RL, Roberts E, Rosen H
JournalJ Biol Chem
PubMed ID17400555
'The clinical immunosuppressant FTY720 is a sphingosine analogue that, once phosphorylated by sphingosine kinase 2 (Sphk2), is an agonist of multiple receptor subtypes for sphingosine 1-phosphate. Short exposures to FTY720 afford long term protection in lymphoproliferative and autoimmune disease models, presumably by inducing apoptosis in subsets of cells essential for ... More
Cyclin D1 repression of nuclear respiratory factor 1 integrates nuclear DNA synthesis and mitochondrial function.
AuthorsWang C, Li Z, Lu Y, Du R, Katiyar S, Yang J, Fu M, Leader JE, Quong A, Novikoff PM, Pestell RG
JournalProc Natl Acad Sci U S A
PubMed ID16864783
'Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. Herein, cyclin D1 deficiency increased mitochondrial size and activity that was rescued by cyclin D1 in a Cdk-dependent manner. Nuclear respiratory factor 1 (NRF-1), which induces nuclear-encoded mitochondrial genes, was repressed in expression and activity ... More
Identification of a new tumor suppressor gene located at chromosome 8p21.3-22.
AuthorsSeibold S, Rudroff C, Weber M, Galle J, Wanner C, Marx M
JournalFASEB J
PubMed ID12692079
'Transformation of normal cells into malignant tumor cells, a process termed carcinogenesis, depends on progressive acquisition of genetic alterations. These result in activation of protooncogenes or inactivation of tumor suppressor genes responsible for the loss of proliferative control in tumor cells and the failure to undergo cellular differentiation. The aim ... More
AuthorsSaffran HA, Pare JM, Corcoran JA, Weller SK, Smiley JR,
JournalEMBO Rep
PubMed ID17186027
'Mitochondria have crucial roles in the life and death of mammalian cells, and help to orchestrate host antiviral defences. Here, we show that the ubiquitous human pathogen herpes simplex virus (HSV) induces rapid and complete degradation of host mitochondrial DNA during productive infection of cultured mammalian cells. The depletion of ... More
Live imaging of mammalian retina: rod outer segments are stained by conventional mitochondrial dyes.
AuthorsBianchini P, Calzia D, Ravera S, Candiano G, Bachi A, Morelli A, Bruschi M, Pepe IM, Diaspro A, Panfoli I,
JournalJ Biomed Opt
PubMed ID19021397
The vertebrate retina is an array of
Functional delivery of a cytosolic tRNA into mutant mitochondria of human cells.
AuthorsMahata B, Mukherjee S, Mishra S, Bandyopadhyay A, Adhya S
JournalScience
PubMed ID17053148
Many maternally inherited and incurable neuromyopathies are caused by mutations in mitochondrial (mt) transfer RNA (tRNA) genes. Kinetoplastid protozoa, including Leishmania, have evolved specialized systems for importing nucleus-encoded tRNAs into mitochondria. We found that the Leishmania RNA import complex (RIC) could enter human cells by a caveolin-1-dependent pathway, where it ... More
Sensitive electrochemical determination of unlabeled MutS protein and detection of point mutations in DNA.
AuthorsPalecek E, Masarík M, Kizek R, Kuhlmeier D, Hassmann J, Schülein J
JournalAnal Chem
PubMed ID15456317
MutS protein plays an important role in the DNA repair system in prokaryotic and eukaryotic cells; it recognizes unpaired and mispaired bases in duplex DNA and can be used for detection of point mutations in vitro. We have shown that small amounts of this protein can be detected electrochemically at ... More
Proline accumulation is inhibitory to Arabidopsis seedlings during heat stress.
AuthorsLv WT, Lin B, Zhang M, Hua XJ,
JournalPlant Physiol
PubMed ID21670222
The effect of proline (Pro) accumulation on heat sensitivity was investigated using transgenic Arabidopsis (Arabidopsis thaliana) plants ectopically expressing the ?(1)-pyrroline-5-carboxylate synthetase 1 gene (AtP5CS1) under the control of a heat shock protein 17.6II gene promoter. During heat stress, the heat-inducible expression of the AtP5CS1 transgene was capable of enhancing ... More
Diabetic cardiomyopathy-associated dysfunction in spatially distinct mitochondrial subpopulations.
AuthorsDabkowski ER, Williamson CL, Bukowski VC, Chapman RS, Leonard SS, Peer CJ, Callery PS, Hollander JM,
JournalAm J Physiol Heart Circ Physiol
PubMed ID19060128
Diabetic cardiomyopathy is the leading cause of heart failure among diabetic patients, and mitochondrial dysfunction has been implicated as an underlying cause in the pathogenesis. Cardiac mitochondria consist of two spatially, functionally, and morphologically distinct subpopulations, termed subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM). SSM are situated beneath the plasma ... More
Tracing of labile zinc in live fish hepatocytes using FluoZin-3.
Intracellular zinc levels are homeostatically regulated and although most is bound, a pool of labile Zn(II) is present in cells. We show here that the zinc probe FluoZin-3 is useful to monitor zinc fluxes during fluorescent imaging of the trout hepatic cell line D11. Nuclei and bulk cytosol appeared to ... More
Hyperactive intracellular calcium signaling associated with localized mitochondrial defects in skeletal muscle of an animal model of amyotrophic lateral sclerosis.
AuthorsZhou J, Yi J, Fu R, Liu E, Siddique T, Ríos E, Deng HX,
JournalJ Biol Chem
PubMed ID19889637
Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disorder characterized by degeneration of motor neurons and atrophy of skeletal muscle. Mutations in the superoxide dismutase (SOD1) gene are linked to 20% cases of inherited ALS. Mitochondrial dysfunction has been implicated in the pathogenic process, but how it contributes to muscle ... More
Stable Golgi-mitochondria complexes and formation of Golgi Ca(2+) gradients in pancreatic acinar cells.
We have determined the localization of the Golgi with respect to other organelles in living pancreatic acinar cells and the importance of this localization to the establishment of Ca(2+) gradients over the Golgi. Using confocal microscopy and the Golgi-specific fluorescent probe 6-((N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoyl)sphingosine, we found Golgi structures localizing to the outer ... More
Super-resolution fluorescence imaging of organelles in live cells with photoswitchable membrane probes.
AuthorsShim SH, Xia C, Zhong G, Babcock HP, Vaughan JC, Huang B, Wang X, Xu C, Bi GQ, Zhuang X,
JournalProc Natl Acad Sci U S A
PubMed ID22891300
Imaging membranes in live cells with nanometer-scale resolution promises to reveal ultrastructural dynamics of organelles that are essential for cellular functions. In this work, we identified photoswitchable membrane probes and obtained super-resolution fluorescence images of cellular membranes. We demonstrated the photoswitching capabilities of eight commonly used membrane probes, each specific ... More
Insoluble, speckled cytosolic distribution of retinoic acid receptor alpha protein as a marker of hepatic stellate cell activation in vitro.
AuthorsMezaki Y, Yamaguchi N, Yoshikawa K, Miura M, Imai K, Itoh H, Senoo H,
JournalJ Histochem Cytochem
PubMed ID19332432
Hepatic stellate cells (HSCs) are the major site of retinoid storage, and their activation is a key process in liver fibrogenesis. We have previously shown that expression of the retinoic acid receptor alpha (RARalpha) is upregulated in activated rat HSCs at a posttranscriptional level and that these RARalpha proteins showed ... More
A common lipid links Mfn-mediated mitochondrial fusion and SNARE-regulated exocytosis.
Fusion of vesicles into target membranes during many types of regulated exocytosis requires both SNARE-complex proteins and fusogenic lipids, such as phosphatidic acid. Mitochondrial fusion is less well understood but distinct, as it is mediated instead by the protein Mitofusin (Mfn). Here, we identify an ancestral member of the phospholipase ... More
Ca2+ -linked upregulation and mitochondrial production of nitric oxide in the mouse preimplantation embryo.
AuthorsManser RC, Houghton FD
JournalJ Cell Sci
PubMed ID16638811
Previous studies have demonstrated a role for the signalling agent nitric oxide in regulating preimplantation embryo development. We have now investigated the biochemical mode of action of nitric oxide in mouse embryos in terms of mitochondrial function and Ca2+ signalling. DETA-NONOate, a nitric oxide donor, decreased day 4 blastocyst cell ... More
Accumulation of endoplasmic membranes and novel membrane-bound ribosome-signal recognition particle receptor complexes in Escherichia coli.
AuthorsHerskovits AA, Shimoni E, Minsky A, Bibi E
JournalJ Cell Biol
PubMed ID12417577
In Escherichia coli, ribosomes must interact with translocons on the membrane for the proper integration of newly synthesized membrane proteins, cotranslationally. Previous in vivo studies indicated that unlike the E. coli signal recognition particle (SRP), the SRP receptor FtsY is required for membrane targeting of ribosomes. Accordingly, a putative SRP-independent, ... More
Characterization of cells with different mitochondrial membrane potential during apoptosis.
AuthorsLugli E, Troiano L, Ferraresi R, Roat E, Prada N, Nasi M, Pinti M, Cooper EL, Cossarizza A
JournalCytometry A
PubMed ID16184612
BACKGROUND: Until now, the simultaneous analysis of several parameters during apoptosis, including DNA content and mitochondrial membrane potential (DeltaPsi), has not been possible because of the spectral characteristics of the commonly used dyes. Using polychromatic flow cytometry based upon multiple laser and UV lamp excitation, we have characterized cells with ... More
Intracellular dissemination of peroxidative stress. Internalization, transport, and lethal targeting of a cholesterol hydroperoxide species by sterol carrier protein-2-overexpressing hepatoma cells.
Sterol carrier protein-2 (SCP-2) plays a crucial role in the trafficking and metabolism of cholesterol and other lipids in mammalian cells. Lipid hydroperoxides generated under oxidative stress conditions are relatively long-lived intermediates that damage cell membranes and play an important role in redox signaling. We hypothesized that SCP-2-facilitated translocation of ... More
Palmitoylation and intracellular domain interactions both contribute to raft targeting of linker for activation of T cells.
AuthorsShogomori H, Hammond AT, Ostermeyer-Fay AG, Barr DJ, Feigenson GW, London E, Brown DA
JournalJ Biol Chem
PubMed ID15753089
Some transmembrane proteins must associate with lipid rafts to function. However, even if acylated, transmembrane proteins should not pack well with ordered raft lipids, and raft targeting is puzzling. Acylation is necessary for raft targeting of linker for activation of T cells (LAT). To determine whether an acylated transmembrane domain ... More
Quantum dot-induced cell death involves Fas upregulation and lipid peroxidation in human neuroblastoma cells.
AuthorsChoi AO, Cho SJ, Desbarats J, Lovric J, Maysinger D
JournalJ Nanobiotechnology
PubMed ID17295922
BACKGROUND: Neuroblastoma, a frequently occurring solid tumour in children, remains a therapeutic challenge as existing imaging tools are inadequate for proper and accurate diagnosis, resulting in treatment failures. Nanoparticles have recently been introduced to the field of cancer research and promise remarkable improvements in diagnostics, targeting and drug delivery. Among ... More
Estrogen exerts a spatial and temporal influence on reactive oxygen species generation that precedes calcium uptake in high-capacity mitochondria: implications for rapid nongenomic signaling of cell growth.
AuthorsParkash J, Felty Q, Roy D
JournalBiochemistry
PubMed ID16503642
Novel findings that emerged from this study underscore the fact that the dynamic nature of mitochondria leads to functional heterogeneity of [Ca(2+)](mito) with respect to estrogen actions in MCF7 cells. We show that estrogen exposure to cells increased [Ca(2+)](mito) in a high-calcium capacity mitochondrial population but not in low-calcium capacity ... More
Defective one- or two-electron reduction of the anticancer anthracycline epirubicin in human heart. Relative importance of vesicular sequestration and impaired efficiency of electron addition.
AuthorsSalvatorelli E, Guarnieri S, Menna P, Liberi G, Calafiore AM, Mariggiò MA, Mordente A, Gianni L, Minotti G
JournalJ Biol Chem
PubMed ID16423826
One-electron quinone reduction and two-electron carbonyl reduction convert the anticancer anthracycline doxorubicin to reactive oxygen species (ROS) or a secondary alcohol metabolite that contributes to inducing a severe form of cardiotoxicity. The closely related analogue epirubicin induces less cardiotoxicity, but the determinants of its different behavior have not been elucidated. ... More
Late Endosomes Act as mRNA Translation Platforms and Sustain Mitochondria in Axons.
Authors
JournalCell
PubMed ID30612743
Enforced PGC-1a expression promotes CD8 T cell fitness, memory formation and antitumor immunity.
AuthorsDumauthioz N, Tschumi B, Wenes M, Marti B, Wang H, Franco F, Li W, Lopez-Mejia IC, Fajas L, Ho PC, Donda A, Romero P, Zhang L
JournalCell Mol Immunol
PubMed ID32055005
'Memory CD8 T cells can provide long-term protection against tumors, which depends on their enhanced proliferative capacity, self-renewal and unique metabolic rewiring to sustain cellular fitness. Specifically, memory CD8 T cells engage oxidative phosphorylation and fatty acid oxidation to fulfill their metabolic demands. In contrast, tumor-infiltrating lymphocytes (TILs) display severe ... More
Mitochondrial fragmentation, elevated mitochondrial superoxide and respiratory supercomplexes disassembly is connected with the tamoxifen-resistant phenotype of breast cancer cells.
AuthorsTomková V, Sandoval-Acuña C, Torrealba N, Truksa J
JournalFree Radic Biol Med
PubMed ID31494243
'Tamoxifen resistance remains a clinical obstacle in the treatment of hormone sensitive breast cancer. It has been reported that tamoxifen is able to target respiratory complex I within mitochondria. Therefore, we established two tamoxifen-resistant cell lines, MCF7 Tam5R and T47D Tam5R resistant to 5?µM tamoxifen and investigated whether tamoxifen-resistant cells ... More
Mitochondrial origins of fractional control in regulated cell death.
AuthorsSantos LC, Vogel R, Chipuk JE, Birtwistle MR, Stolovitzky G, Meyer P
JournalNat Commun
PubMed ID30899020
'Individual cells in clonal populations often respond differently to environmental changes; for binary phenotypes, such as cell death, this can be measured as a fractional response. These types of responses have been attributed to cell-intrinsic stochastic processes and variable abundances of biochemical constituents, such as proteins, but the influence of ... More
High metabolic rate and stem cell characteristics of esophageal cancer stem-like cells depend on the Hsp27-AKT-HK2 pathway.
AuthorsLiu CC, Chou KT, Hsu JW, Lin JH, Hsu TW, Yen DH, Hung SC, Hsu HS
JournalInt J Cancer
PubMed ID30920655
'Tumor progression with chemoresistance and local recurrence is commonly happened during treatment of esophageal squamous cell carcinoma (ESCC). Cancer stem cells (CSC) may respond for tumor progression. However, there are few reports regarding metabolism of esophageal CSCs with clinical correlation. In this work, we demonstrated that ESCC cell lines in ... More
Stanniocalcin 1 is a phagocytosis checkpoint driving tumor immune resistance.
Authors
JournalCancer Cell
PubMed ID33513345
Proteomics of Melanoma Response to Immunotherapy Reveals Mitochondrial Dependence.
Authors
JournalCell
PubMed ID31495571
Cell Type Purification by Single-Cell Transcriptome-Trained Sorting.
Authors
JournalCell
PubMed ID31585086
Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis.
Authors
JournalCell
PubMed ID29909986
In vivo CRISPR screening reveals nutrient signaling processes underpinning CD8+ T cell fate decisions.
Authors
JournalCell
PubMed ID33636132
A Common Embryonic Origin of Stem Cells Drives Developmental and Adult Neurogenesis.
Authors
JournalCell
PubMed ID30929900
Treg Cells Promote the SREBP1-Dependent Metabolic Fitness of Tumor-Promoting Macrophages via Repression of CD8+ T Cell-Derived Interferon-γ.
Authors
JournalImmunity
PubMed ID31350177
Oxysterol Restraint of Cholesterol Synthesis Prevents AIM2 Inflammasome Activation.
Authors
JournalCell
PubMed ID29033131
PDH-mediated metabolic flow is critical for skeletal muscle stem cell differentiation and myotube formation during regeneration in mice.
AuthorsHori S, Hiramuki Y, Nishimura D, Sato F, Sehara-Fujisawa A
JournalFASEB J
PubMed ID30939245
Skeletal muscle satellite cells (SMSCs), the major stem cells responsible for the regeneration of skeletal muscle, are normally cell cycle arrested but differentiate to generate myocytes upon muscle damage, forming new myofibers along with self-renewing stem cells in preparation for subsequent injury. In this study, we investigated which factors stimulate ... More
Oncolytic Viruses Engineered to Enforce Leptin Expression Reprogram Tumor-Infiltrating T Cell Metabolism and Promote Tumor Clearance.
AuthorsRivadeneira DB, DePeaux K, Wang Y, Kulkarni A, Tabib T, Menk AV, Sampath P, Lafyatis R, Ferris RL, Sarkar SN, Thorne SH, Delgoffe GM
JournalImmunity
PubMed ID31471106
Immunotherapy can reinvigorate dormant responses to cancer, but response rates remain low. Oncolytic viruses, which replicate in cancer cells, induce tumor lysis and immune priming, but their immune consequences are unclear. We profiled the infiltrate of aggressive melanomas induced by oncolytic Vaccinia virus using RNA sequencing and found substantial remodeling ... More
Pentamidine inhibits prostate cancer progression via selectively inducing mitochondrial DNA depletion and dysfunction.
AuthorsLiu L, Wang F, Tong Y, Li LF, Liu Y, Gao WQ
JournalCell Prolif
PubMed ID31721355
We investigated the anti-cancer activity of pentamidine, an anti-protozoal cationic aromatic diamidine drug, in prostate cancer cells and aimed to provide valuable insights for improving the efficacy of prostate cancer treatment. ... More