A hyperfused mitochondrial state achieved at G1-S regulates cyclin E buildup and entry into S phase.
AuthorsMitra K, Wunder C, Roysam B, Lin G, Lippincott-Schwartz J,
JournalProc Natl Acad Sci U S A
PubMed ID19617534
Mitochondria undergo fission-fusion events that render these organelles highly dynamic in cells. We report a relationship between mitochondrial form and cell cycle control at the G(1)-S boundary. Mitochondria convert from isolated, fragmented elements into a hyperfused, giant network at G(1)-S transition. The network is electrically continuous and has greater ATP ... More
Antiapoptotic effect of nicorandil mediated by mitochondrial atp-sensitive potassium channels in cultured cardiac myocytes.
AuthorsAkao M, Teshima Y, Marbán E
JournalJ Am Coll Cardiol
PubMed ID12204514
OBJECTIVES: We examined whether nicorandil, a clinically useful drug for the treatment of ischemic syndromes, inhibits myocardial apoptosis. BACKGROUND: Nicorandil has been reported to have a cardioprotective action through activation of mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels. Based on our recent observation that mitoK(ATP) channel activation has a remarkable antiapoptotic effect ... More
Synaptic mitochondria are more susceptible to Ca2+overload than nonsynaptic mitochondria.
AuthorsBrown MR, Sullivan PG, Geddes JW
JournalJ Biol Chem
PubMed ID16517608
'Mitochondria in nerve terminals are subjected to extensive Ca2+ fluxes and high energy demands, but the extent to which the synaptic mitochondria buffer Ca2+ is unclear. In this study, we identified a difference in the Ca2+ clearance ability of nonsynaptic versus synaptic mitochondrial populations enriched from rat cerebral cortex. Mitochondria ... More
Age-related macular degeneration. The lipofusion component N-retinyl-N-retinylidene ethanolamine detaches proapoptotic proteins from mitochondria and induces apoptosis in mammalian retinal pigment epithelial cells.
AuthorsSuter M, Remé C, Grimm C, Wenzel A, Jäättela M, Esser P, Kociok N, Leist M, Richter C
JournalJ Biol Chem
PubMed ID11006290
'10-20% of individuals over the age of 65 suffer from age-related macular degeneration (AMD), the leading cause of severe visual impairment in humans living in developed countries. The pathogenesis of this complex disease is poorly understood, and no efficient therapy or prevention exists to date. A precondition for AMD appears ... More
VDAC-dependent permeabilization of the outer mitochondrial membrane by superoxide induces rapid and massive cytochrome c release.
AuthorsMadesh M, Hajnóczky G
JournalJ Cell Biol
PubMed ID11739410
'Enhanced formation of reactive oxygen species (ROS), superoxide (O2*-), and hydrogen peroxide (H2O2) may result in either apoptosis or other forms of cell death. Here, we studied the mechanisms underlying activation of the apoptotic machinery by ROS. Exposure of permeabilized HepG2 cells to O2*- elicited rapid and massive cytochrome c ... More
Involvement of mitochondrial signaling pathways in the mechanism of Fas-mediated apoptosis after spinal cord injury.
AuthorsYu WR, Liu T, Fehlings TK, Fehlings MG,
JournalEur J Neurosci
PubMed ID19120440
'Activation of the Fas receptor has been recently linked to apoptotic cell death after spinal cord injury (SCI). Although it is generally considered that Fas activation mediates apoptosis predominantly through the extrinsic pathway, we hypothesized that intrinsic mitochondrial signaling could be involved in the underlying mechanism of Fas-induced apoptosis after ... More
Reactive oxygen species (ROS)-induced ROS release: a new phenomenon accompanying induction of the mitochondrial permeability transition in cardiac myocytes.
'We sought to understand the relationship between reactive oxygen species (ROS) and the mitochondrial permeability transition (MPT) in cardiac myocytes based on the observation of increased ROS production at sites of spontaneously deenergized mitochondria. We devised a new model enabling incremental ROS accumulation in individual mitochondria in isolated cardiac myocytes ... More
The influenza A virus PB1-F2 protein targets the inner mitochondrial membrane via a predicted basic amphipathic helix that disrupts mitochondrial function.
'The 11th influenza A virus gene product is an 87-amino-acid protein provisionally named PB1-F2 (because it is encoded by an open reading frame overlapping the PB1 open reading frame). A significant fraction of PB1-F2 localizes to the inner mitochondrial membrane in influenza A virus-infected cells. PB1-F2 appears to enhance virus-induced ... More
Herp stabilizes neuronal Ca2+ homeostasis and mitochondrial function during endoplasmic reticulum stress.
AuthorsChan SL, Fu W, Zhang P, Cheng A, Lee J, Kokame K, Mattson MP
JournalJ Biol Chem
PubMed ID15102845
'In response to endoplasmic reticulum (ER) stress, cells launch homeostatic and protective responses, but can also activate cell death cascades. A 54 kDa integral ER membrane protein called Herp was identified as a stress-responsive protein in non-neuronal cells. We report that Herp is present in neurons in the developing and ... More
'Synaptically released Zn2+ can enter and cause injury to postsynaptic neurons. Microfluorimetric studies using the Zn2+-sensitive probe, Newport green, examined levels of [Zn2+]i attained in cultured cortical neurons on exposure to N-methyl-D-asparte, kainate, or high K+ (to activate voltage-sensitive Ca2+ channels) in the presence of 300 microM Zn2+. Indicating particularly ... More
Correlated three-dimensional light and electron microscopy reveals transformation of mitochondria during apoptosis.
AuthorsSun MG, Williams J, Munoz-Pinedo C, Perkins GA, Brown JM, Ellisman MH, Green DR, Frey TG
JournalNat Cell Biol
PubMed ID17721514
'In addition to their role in cellular bioenergetics, mitochondria also initiate common forms of programmed cell death (apoptosis) through the release of proteins such as cytochrome c from the intermembrane and intracristal spaces. The release of these proteins is studied in populations of cells by western blotting mitochondrial and cytoplasmic ... More
Flow cytometric determination of mitochondrial membrane potential changes during apoptosis of T lymphocytic and pancreatic beta cell lines: comparison of tetramethylrhodamineethylester (TMRE), chloromethyl-X-rosamine (H2-CMX-Ros) and MitoTracker Red 580 (MTR580).
AuthorsJayaraman S
JournalJ Immunol Methods
PubMed ID16256133
'The mitochondria-specific dyes, TMRE, H2-CMX-Ros and MTR580 were determined for their suitability to measure mitochondrial potential changes of the T cell leukemia cell line Jurkat and insulin-secreting beta cell line NIT-1 during apoptosis. Both freshly harvested Jurkat and NIT-1 cells induced to undergo apoptosis displayed poor retention of the potential-sensitive, ... More
Striatal cells from mutant huntingtin knock-in mice are selectively vulnerable to mitochondrial complex II inhibitor-induced cell death through a non-apoptotic pathway.
AuthorsRuan Q, Lesort M, MacDonald ME, Johnson GV
JournalHum Mol Genet
PubMed ID14962977
'Extensive striatal neuronal loss occurs in Huntington''s disease (HD), which is caused by an expanded polyglutamine tract in huntingtin (htt). Evidence suggests that mutant htt directly or indirectly compromises mitochondrial function, contributing to the neuronal loss. To determine the role of compromised mitochondrial function in the neuronal cell death in ... More
Mitochondria are morphologically heterogeneous within cells.
AuthorsCollins TJ, Bootman MD
JournalJ Exp Biol
PubMed ID12756281
'Mitochondria play key roles in the life and death of cells. We investigated whether mitochondria represent morphologically continuous entities within single intact cells. Physical continuity of mitochondria was determined by three-dimensional reconstruction of fluorescence from mitochondrially targeted DsRed1 or tetra-methyl rhodamine ethyl ester (TMRE). The mitochondria of pancreatic acinar, porcine ... More
Measurement of mitochondrial membrane potential using fluorescent rhodamine derivatives.
AuthorsScaduto RC, Grotyohann LW
JournalBiophys J
PubMed ID9876159
'We investigated the use of rhodamine 123 (R123), tetramethylrhodamine methyl ester (TMRM), and tetramethylrhodamine ethyl ester (TMRE) as fluorescent probes to monitor the membrane potential of mitochondria. These indicator dyes are lipophilic cations accumulated by mitochondria in proportion to DeltaPsi. Upon accumulation, all three dyes exhibit a red shift in ... More
Stimulation-evoked increases in cytosolic [Ca(2+)] in mouse motor nerve terminals are limited by mitochondrial uptake and are temperature-dependent.
AuthorsDavid G, Barrett EF
JournalJ Neurosci
PubMed ID11007886
'Increases in cytosolic [Ca(2+)] evoked by trains of action potentials (20-100 Hz) were recorded from mouse and lizard motor nerve terminals filled with a low-affinity fluorescent indicator, Oregon Green BAPTA 5N. In mouse terminals at near-physiological temperatures (30-38 degrees C), trains of action potentials at 25-100 Hz elicited increases in ... More
ADP regulates movements of mitochondria in neurons.
AuthorsMironov SL
JournalBiophys J
PubMed ID17277190
'Mitochondria often reside in subcellular regions with high metabolic demands. We examined the mechanisms that can govern the relocation of mitochondria to these sites in respiratory neurons. Mitochondria were visualized using tetramethylrhodamineethylester, and their movements were analyzed by applying single-particle tracking. Intracellular ATP ([ATP](i)) was assessed by imaging the luminescence ... More
Bax translocation and mitochondrial fragmentation induced by Helicobacter pylori.
AuthorsAshktorab H, Frank S, Khaled AR, Durum SK, Kifle B, Smoot DT
JournalGut
PubMed ID15138206
'BACKGROUND AND AIMS: Previous in vitro and in vivo studies have revealed an association between Helicobacter pylori infection and apoptosis in gastric epithelial cells. Although involvement of the Bcl-2 family of proteins as well as cytochrome c release has been demonstrated in H pylori induced cell death, the exact role ... More
The mitochondrial membrane potential and Ca2+ oscillations in smooth muscle.
AuthorsChalmers S, McCarron JG,
JournalJ Cell Sci
PubMed ID18073239
'Ca2+ uptake by mitochondria might both modulate the cytosolic Ca2+ concentration ([Ca2+]c) and depolarize the mitochondrial membrane potential (delta Psi m) to limit ATP production. To investigate how physiological Ca2+ signaling might affect energy production, delta Psi m was examined during Ca2+ oscillations in smooth muscle cells. In single, voltage-clamped ... More
Methods for the assessment of mitochondrial membrane permeabilization in apoptosis.
AuthorsGalluzzi L, Zamzami N, de La Motte Rouge T, Lemaire C, Brenner C, Kroemer G
JournalApoptosis
PubMed ID17294081
'Mitochondrial membrane permeabilization (MMP) is considered as the "point-of-no-return" in numerous models of programmed cell death. Indeed, mitochondria determine the intrinsic pathway of apoptosis, and play a major role in the extrinsic route as well. MMP affects the inner and outer mitochondrial membranes (IM and OM, respectively) to a variable ... More
Metabolic consequences of functional complexes of mitochondria, myofibrils and sarcoplasmic reticulum in muscle cells.
AuthorsAndrienko T, Kuznetsov AV, Kaambre T, Usson Y, Orosco A, Appaix F, Tiivel T, Sikk P, Vendelin M, Margreiter R, Saks VA
JournalJ Exp Biol
PubMed ID12756288
'Regulation of mitochondrial respiration both by endogenous and exogenous ADP in the cells in situ was studied in isolated and permeabilized cardiomyocytes, permeabilized cardiac fibers and ''ghost'' fibers (all with a diameter of 10-20 micro m) at different (0-3 micro moll(-1)) free Ca(2+) concentrations in the medium. In all these ... More
Comparison of the effect of mitochondrial inhibitors on mitochondrial membrane potential in two different cell lines using flow cytometry and spectrofluorometry.
AuthorsKalbácová M, Vrbacký M, Drahota Z, Melková Z
JournalCytometry A
PubMed ID12655654
'BACKGROUND: Determination of mitochondrial membrane potential (DeltaPsim) is widely used to characterize cellular metabolism, viability, and apoptosis. Changes of DeltaPsim induced by inhibitors of oxidative phosphorylation characterize respective contributions of mitochondria and glycolysis to adenosine triphosphate (ATP) synthesis. METHODS: DeltaPsim in BSC-40 and HeLa G cell lines was determined by ... More
Lysosomal destabilization in p53-induced apoptosis.
AuthorsYuan XM, Li W, Dalen H, Lotem J, Kama R, Sachs L, Brunk UT
JournalProc Natl Acad Sci U S A
PubMed ID11959917
'The tumor suppressor wild-type p53 can induce apoptosis. M1-t-p53 myeloid leukemic cells have a temperature-sensitive p53 protein that changes its conformation to wild-type p53 after transfer from 37 degrees C to 32 degrees C. We have now found that these cells showed an early lysosomal rupture after transfer to 32 ... More
Bcl-x(L) prevents the initial decrease in mitochondrial membrane potential and subsequent reactive oxygen species production during tumor necrosis factor alpha-induced apoptosis.
AuthorsGottlieb E, Vander Heiden MG, Thompson CB
JournalMol Cell Biol
PubMed ID10891504
'The Bcl-2 family of proteins are involved in regulating the redox state of cells. However, the mode of action of Bcl-2 proteins remains unclear. This work analyzed the effects of Bcl-x(L) on the cellular redox state after treatment with tumor necrosis factor alpha (TNF-alpha) or exogenous oxidants. We show that ... More
A high-throughput assay for mitochondrial membrane potential in permeabilized yeast cells.
AuthorsFarrelly E, Amaral MC, Marshall L, Huang SG
JournalAnal Biochem
PubMed ID11399043
'A fluorometric assay for mitochondrial membrane potential in permeabilized yeast cells has been developed. This method involves permeabilizing the plasma membrane and measuring the distribution of a mitochondrial membrane potential sensitive probe 3,3''-dipropylthiadicarbocyanine iodide (DiSC(3)(5); DiSC(3)). In permeabilized cells, DiSC(3) fluorescence decreased when introduced into energized mitochondria and increased three- ... More
A test of the singlet oxygen mechanism of cationic dye photosensitization of mitochondrial damage.
AuthorsBunting JR
JournalPhotochem Photobiol
PubMed ID1603852
'Aromatic cationic dyes have a potential as photo-chemotherapeutic agents because they are selectively concentrated into the mitochondria of cancerous cells. The mechanism of cytophototoxicity has been proposed to be primarily due to dye sensitized photogeneration of highly toxic singlet oxygen (1O2) at the mitochondria. We tested this hypothesis by measuring ... More
Intracellular sodium modulates mitochondrial calcium signaling in vascular endothelial cells.
AuthorsSedova M, Blatter LA
JournalJ Biol Chem
PubMed ID10958797
'We have investigated the role of extramitochondrial Na(+) for the regulation of mitochondrial Ca(2+) concentration ([Ca(2+)](m)) in permeabilized single vascular endothelial cells. [Ca(2+)](m) was measured by loading the cells with the membrane-permeant Ca(2+) indicator fluo-3/AM and subsequent removal of cytoplasmic fluo-3 by surface membrane permeabilization with digitonin. An elevation of ... More
'Huntington disease (HD) is caused by a pathological elongation of CAG repeats in the huntingtin protein gene and is characterized by atrophy and neuronal loss primarily in the striatum. Mitochondrial dysfunction and impaired Ca2+ homeostasis in HD have been suggested previously. Here, we elucidate the effects of Ca2+ on mitochondria ... More
Mitochondrial ATP-dependent potassium channels: novel effectors of cardioprotection?
AuthorsLiu Y, Sato T, O'Rourke B, Marban E
JournalCirculation
PubMed ID9641699
'BACKGROUND: Brief interruptions of coronary blood flow paradoxically protect the heart from subsequent prolonged ischemia. The basis of such endogenous cardioprotection, known as "ischemic preconditioning," remains uncertain. Pharmacological evidence has implicated ATP-dependent potassium (KATP) channels in the mechanism of preconditioning; however, the effects of sarcolemmal KATP channels on excitability cannot ... More
Application of a high-content multiparameter cytotoxicity assay to prioritize compounds based on toxicity potential in humans.
AuthorsAbraham VC, Towne DL, Waring JF, Warrior U, Burns DJ,
JournalJ Biomol Screen
PubMed ID18566484
'Prioritization of compounds based on human hepatotoxicity potential is currently a key unmet need in drug discovery, as it can become a major problem for several lead compounds in later stages of the drug discovery pipeline. The authors report the validation and implementation of a high-content multiparametric cytotoxicity assay based ... More
Examining intracellular organelle function using fluorescent probes: from animalcules to quantum dots.
AuthorsZorov DB, Kobrinsky E, Juhaszova M, Sollott SJ
JournalCirc Res
PubMed ID15297386
'Fluorescence microscopy imaging has become one of the most useful techniques to assess the activity of individual cells, subcellular trafficking of signals to and between organelles, and to appreciate how organelle function is regulated. The past 2 decades have seen a tremendous advance in the rational design and development in ... More
Emodin enhances arsenic trioxide-induced apoptosis via generation of reactive oxygen species and inhibition of survival signaling.
AuthorsYi J, Yang J, He R, Gao F, Sang H, Tang X, Ye RD
JournalCancer Res
PubMed ID14729614
'Although arsenic trioxide (As(2)O(3)) induces apoptosis in a relatively wide spectrum of tumors, the sensitivity of different cell types to this treatment varies to a great extent. Because reactive oxygen species (ROS) are critically involved in As(2)O(3)-induced apoptosis, we attempted to explore the possibility that elevating the cellular ROS level ... More
Role of superoxide, nitric oxide, and peroxynitrite in doxorubicin-induced cell death in vivo and in vitro.
AuthorsMukhopadhyay P, Rajesh M, Bátkai S, Kashiwaya Y, Haskó G, Liaudet L, Szabó C, Pacher P,
JournalAm J Physiol Heart Circ Physiol
PubMed ID19286953
'Doxorubicin (DOX) is a potent available antitumor agent; however, its clinical use is limited because of its cardiotoxicity. Cell death is a key component in DOX-induced cardiotoxicity, but its mechanisms are elusive. Here, we explore the role of superoxide, nitric oxide (NO), and peroxynitrite in DOX-induced cell death using both ... More
Control of InsP3-induced Ca2+ oscillations in permeabilized blowfly salivary gland cells: contribution of mitochondria.
AuthorsZimmermann B
JournalJ Physiol
PubMed ID10856123
'Many agonists linked to the generation of inositol 1,4, 5-trisphosphate (InsP3) and release of Ca2+ from intracellular stores induce repetitive transients in cytosolic Ca2+ whose frequency increases over a certain range of agonist concentrations. In order to investigate the mechanisms underlying this frequency modulation, the fluorescent Ca2+ sensor mag-fura-2 was ... More
Notch4 inhibits endothelial apoptosis via RBP-Jkappa-dependent and -independent pathways.
AuthorsMacKenzie F, Duriez P, Wong F, Noseda M, Karsan A
JournalJ Biol Chem
PubMed ID14701863
'Notch4, a member of the Notch family of transmembrane receptors, is expressed primarily on endothelial cells. Activation of Notch in various cell systems has been shown to regulate cell fate decisions, partly by regulating the propensity of cells to live or die. Various studies have demonstrated a role for Notch1 ... More
Preservation of mitochondrial structure and function after Bid- or Bax-mediated cytochrome c release.
Authorsvon Ahsen O, Renken C, Perkins G, Kluck RM, Bossy-Wetzel E, Newmeyer DD
JournalJ Cell Biol
PubMed ID10973993
'Proapoptotic members of the Bcl-2 protein family, including Bid and Bax, can activate apoptosis by directly interacting with mitochondria to cause cytochrome c translocation from the intermembrane space into the cytoplasm, thereby triggering Apaf-1-mediated caspase activation. Under some circumstances, when caspase activation is blocked, cells can recover from cytochrome c ... More
Intracellular fluorescent probe concentrations by confocal microscopy.
AuthorsFink C, Morgan F, Loew LM
JournalBiophys J
PubMed ID9746507
'A general method is described that takes advantage of the optical sectioning properties of a confocal microscope to enable measurement of both absolute and relative concentrations of fluorescent molecules inside cells. For compartments within cells that are substantially larger than the point spread function, the fluorescence intensity is simply proportional ... More
Heat shock induces apoptosis independently of any known initiator caspase-activating complex.
AuthorsMilleron RS, Bratton SB
JournalJ Biol Chem
PubMed ID16618700
'Adaptive responses to mild heat shock are among the most widely conserved and studied in nature. More intense heat shock, however, induces apoptosis through mechanisms that remain largely unknown. Herein, we present evidence that heat shock activates an apical protease that stimulates mitochondrial outer membrane permeabilization and processing of the ... More
Imaging in five dimensions: time-dependent membrane potentials in individual mitochondria.
AuthorsLoew LM, Tuft RA, Carrington W, Fay FS
JournalBiophys J
PubMed ID8312478
'Because of its importance in the chemiosmotic theory, mitochondrial membrane potential has been the object of many investigations. Significantly, however, quantitative data on how energy transduction might be regulated or perturbed by the physiological state of the cell has only been gathered via indirect studies on isolated mitochondrial suspensions; quantitative ... More
Mitochondria play no roles in Mn(II)-induced apoptosis in HeLa cells.
AuthorsOubrahim H, Stadtman ER, Chock PB
JournalProc Natl Acad Sci U S A
PubMed ID11493712
'Manganese(II) has been shown to exhibit catalase-like activity under physiological conditions. In the course of studies to test the antioxidant activity of Mn(II) on HeLa cells, it was observed at high concentrations (1-2 mM) that Mn(II) also induced apoptosis, as judged by changes in cell morphology, caspase-3 activation, cleavage of ... More
Mitochondria exert a negative feedback on the propagation of intracellular Ca2+ waves in rat cortical astrocytes.
AuthorsBoitier E, Rea R, Duchen MR
JournalJ Cell Biol
PubMed ID10330407
'We have used digital fluorescence imaging techniques to explore the interplay between mitochondrial Ca2+ uptake and physiological Ca2+ signaling in rat cortical astrocytes. A rise in cytosolic Ca2+ ([Ca2+]cyt), resulting from mobilization of ER Ca2+ stores was followed by a rise in mitochondrial Ca2+ ([Ca2+]m, monitored using rhod-2). Whereas [Ca2+]cyt ... More
Quantification of calcium signal transmission from sarco-endoplasmic reticulum to the mitochondria.
AuthorsPacher P, Csordás P, Schneider T, Hajnóczky G
JournalJ Physiol
PubMed ID11118489
'Recent studies have shown that ryanodine and IP3 receptor (RyR/IP3R)-mediated cytosolic Ca2+ signals propagate to the mitochondria, initiating chains of events vital in the regulation of different cellular functions. However, the fraction of released Ca2+ utilized by the mitochondria during these processes has not been quantified. To measure the amount ... More
Characterization of novel UCP5/BMCP1 isoforms and differential regulation of UCP4 and UCP5 expression through dietary or temperature manipulation.
AuthorsYu XX, Mao W, Zhong A, Schow P, Brush J, Sherwood SW, Adams SH, Pan G
JournalFASEB J
PubMed ID10928996
'Mitochondrial uncoupling proteins have been implicated in the maintenance of metabolic rate and adaptational thermoregulation. We recently reported the identification of a brain-specific mitochondrial uncoupling protein homologue, UCP4. Here we characterized another newly described member of the uncoupling protein family, termed UCP5 (also called BMCP1). UCP5 transcripts are present in ... More
Permeability transition pore regulates both mitochondrial membrane potential and agonist-evoked Ca2+ signals in oligodendrocyte progenitors.
AuthorsSmaili SS, Russell JT
JournalCell Calcium
PubMed ID10598276
'In this study, we investigated the importance of mitochondrial permeability transition pore (PTP) in agonist-evoked cytosolic Ca2+ ([Ca2+]c) signals in oligodendrocyte progenitor cells (OP cells). We measured transmembrane potential across the mitochondrial inner membrane (delta psi m) and [Ca2+]c in the immediate vicinity simultaneously using tetramethylrhodamine ethyl ester (TMRE) and ... More
Abnormal intracellular calcium homeostasis in sympathetic neurons from young prehypertensive rats.
AuthorsLi D, Lee CW, Buckler K, Parekh A, Herring N, Paterson DJ,
JournalHypertension
PubMed ID22252398
'Hypertension is associated with cardiac noradrenergic hyperactivity, although it is not clear whether this precedes or follows the development of hypertension itself. We hypothesized that Ca(2+) homeostasis in postganglionic sympathetic neurons is impaired in spontaneously hypertensive rats (SHRs) and may occur before the development of hypertension. The depolarization-induced rise in ... More
Live intracellular super-resolution imaging using site-specific stains.
AuthorsCarlini L, Manley S,
Journal
PubMed ID24079385
'Point localization super-resolution imaging (SR) requires dyes that can cycle between fluorescent and dark states, in order for their molecular positions to be localized and create a reconstructed image. Dyes should also densely decorate biological features of interest to fully reveal structures being imaged. We tested site-specific dyes in several ... More
Bcl-2 functionally interacts with inositol 1,4,5-trisphosphate receptors to regulate calcium release from the ER in response to inositol 1,4,5-trisphosphate.
'Inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) are channels responsible for calcium release from the endoplasmic reticulum (ER). We show that the anti-apoptotic protein Bcl-2 (either wild type or selectively localized to the ER) significantly inhibited InsP3-mediated calcium release and elevation of cytosolic calcium in WEHI7.2 T cells. This inhibition was due ... More
Kinetic analysis of rhodamines efflux mediated by the multidrug resistance protein (MRP1).
AuthorsSaengkhae C, Loetchutinat C, Garnier-Suillerot A
JournalBiophys J
PubMed ID12944313
'Characterization of rhodamine 123 as functional assay for MDR has been primarily focused on P-glycoprotein-mediated MDR. Several studies have suggested that Rh123 is also a substrate for MRP1. However, no quantitative studies of the MRP1-mediated efflux of rhodamines have, up to now, been performed. Measurement of the kinetic characteristics of ... More
Fluctuations in mitochondrial membrane potential caused by repetitive gating of the permeability transition pore.
AuthorsHüser J, Blatter LA
JournalBiochem J
PubMed ID10510294
'Confocal laser scanning microscopy and the potentiometric fluorescence probe tetramethylrhodamine ethyl ester were used to measure changes in membrane electrical potential (DeltaPsi(m)) in individual mitochondria after isolation or in the living cell. Recordings averaged over small mitochondrial populations revealed a gradual decline in DeltaPsi(m) caused by the light-induced generation of ... More
Hyperammonemia inhibits platelet aggregation in rats.
AuthorsShinya H, Matsuo N, Takeyama N, Tanaka T
JournalThromb Res
PubMed ID8822134
'The effect of hyperammonemia on ex vivo platelet function and in vivo nitric oxide synthesis was evaluated in rats. In addition, mitochondrial energy production was assessed from the fluorescence intensity of tetramethylrhodamine ethyl ester (TMRE). Continuous ammonium acetate infusion significantly reduced ex vivo platelet aggregation concomitant with a decrease of ... More
In situ biochemical demonstration that P-glycoprotein is a drug efflux pump with broad specificity.
AuthorsChen Y, Simon SM
JournalJ Cell Biol
PubMed ID10704438
'While P-glycoprotein (Pgp) is the most studied protein involved in resistance to anti-cancer drugs, its mechanism of action is still under debate. Studies of Pgp have used cell lines selected with chemotherapeutics which may have developed many mechanisms of resistance. To eliminate the confounding effects of drug selection on understanding ... More
Monitoring simultaneous subcellular events in vitro by means of coherent multiprobe fluorescence.
AuthorsPlymale DR, Haskins JR, de la Iglesia FA
JournalNat Med
PubMed ID10086396
Confocal microscopy of potentiometric fluorescent dyes.
AuthorsLoew LM
JournalMethods Cell Biol
PubMed ID8246781
Assessment of mitochondrial membrane potential in situ using single potentiometric dyes and a novel fluorescence resonance energy transfer technique.
AuthorsDykens JA, Stout AK
JournalMethods Cell Biol
PubMed ID11381600
Oxidant-induced inhibition of the plasma membrane Ca2+-ATPase in pancreatic acinar cells: role of the mitochondria.
AuthorsBaggaley EM, Elliott AC, Bruce JI,
JournalAm J Physiol Cell Physiol
PubMed ID18787078
Impairment of the normal spatiotemporal pattern of intracellular Ca(2+) ([Ca(2+)](i)) signaling, and in particular, the transition to an irreversible
Measuring apoptosis at the single cell level.
AuthorsBouchier-Hayes L, Muñoz-Pinedo C, Connell S, Green DR,
JournalMethods
PubMed ID18314052
The use of live cell microscopy has made a number of contributions to the study of apoptosis. Many of the tools and techniques are available that allow us to image the key events that occur during cell death including mitochondrial outer membrane permeabilization, mitochondrial transmembrane potential changes, translocation of Bcl-2 ... More
Mitochondrial membrane potential and neuronal glutamate excitotoxicity: mortality and millivolts.
AuthorsNicholls DG, Ward MW
JournalTrends Neurosci
PubMed ID10717676
In the past few years it has become apparent that mitochondria have an essential role in the life and death of neuronal and non-neuronal cells. The central mitochondrial bioenergetic parameter is the protonmotive force, Deltap. Much research has focused on the monitoring of the major component of Deltap, the mitochondrial ... More
Selective loading of Rhod 2 into mitochondria shows mitochondrial Ca2+ transients during the contractile cycle in adult rabbit cardiac myocytes.
AuthorsTrollinger DR, Cascio WE, Lemasters JJ
JournalBiochem Biophys Res Commun
PubMed ID9245725
A strategy of cold loading of the Ca2+-indicating fluorophore Rhod 2-AM followed by warm incubation was developed to selectively label mitochondria of adult rabbit cardiac myocytes. After electrical stimulation, mitochondrial Rhod 2 fluorescence observed by confocal microscopy increased and then rapidly decayed to baseline. In regions between mitochondria, the fluorescent ... More
Mitochondrial transfer between cells can rescue aerobic respiration.
AuthorsSpees JL, Olson SD, Whitney MJ, Prockop DJ
JournalProc Natl Acad Sci U S A
PubMed ID16432190
Current theory indicates that mitochondria were obtained 1.5 billion years ago from an ancient prokaryote. The mitochondria provided the capacity for aerobic respiration, the creation of the eukaryotic cell, and eventually complex multicellular organisms. Recent reports have found that mitochondria play essential roles in aging and determining lifespan. A variety ... More
A pool of extramitochondrial frataxin that promotes cell survival.
AuthorsCondò I, Ventura N, Malisan F, Tomassini B, Testi R
JournalJ Biol Chem
PubMed ID16608849
Frataxin is a mitochondrial protein involved in iron metabolism. Defective expression of frataxin causes Friedreich ataxia (FA), an inherited degenerative syndrome characterized by ataxia, cardiomyopathy, and high incidence of diabetes. Here we report that frataxin-deficient cells are more prone to undergo stress-induced mitochondrial damage and apoptosis, while the overexpression of ... More
Three fluorescent probes for the flow-cytometric assessment of membrane potential in Saccharomyces cerevisiae.
AuthorsDenksteinová B, Sigler K, Plaásek J
JournalFolia Microbiol (Praha)
PubMed ID9449773
Three fluorescent probes, tetramethyl rhodamine ethyl ester (TMRE), 3,3'-dipropylthiacarbocyanine iodide (diS-C3(3)) and 3,3'-dipropyloxacarbocyanine iodide (diO-C3(3)), were tested for their suitability as fluorescent indicators of membrane potential in Saccharomyces cerevisiae in studies performed by flow cytometry. For all these dyes the intensity of fluorescence of stained cells increased with probe concentration ... More
Calcium, a ubiquitous second messenger, stimulates the activity of several mitochondrial dehydrogenases. This has led to the suggestion that the same messenger that signals cell activation could also activate mitochondrial electron/proton transport, thereby meeting demands for increased cellular energy. To test this in live cells, quantitative three-dimensional microscopy and ratio ... More
Granzyme M mediates a novel form of perforin-dependent cell death.
AuthorsKelly JM, Waterhouse NJ, Cretney E, Browne KA, Ellis S, Trapani JA, Smyth MJ
JournalJ Biol Chem
PubMed ID15028722
Cell death is mediated by cytotoxic lymphocytes through various granule serine proteases released with perforin. The unique protease activity, restricted expression, and distinct gene locus of granzyme M suggested this enzyme might have a novel biological function or trigger a novel form of cell death. Herein, we demonstrate that in ... More
Mitochondrial-dependent manganese neurotoxicity in rat primary astrocyte cultures.
AuthorsYin Z, Aschner JL, dos Santos AP, Aschner M,
JournalBrain Res
PubMed ID18313649
Chronic exposure to excessive levels of Mn results in a movement disorder termed manganism, which resembles Parkinson's disease (PD). The pathogenic mechanisms underlying this disorder are not fully understood. Several lines of evidence implicate astrocytes as an early target of Mn neurotoxicity. In the present study, we investigated the effects ... More
Different molecular mechanisms involved in spontaneous and oxidative stress-induced mitochondrial fragmentation in TriPeptidyl Peptidase-1 (TPP-1) deficient fibroblasts.
AuthorsVan Beersel G, Tihon E, Demine S, Hamer I, Jadot M, Arnould T,
JournalBiosci Rep
PubMed ID23249249
The Neuronal Ceroid Lipofuscinosis (NCLs) form a group of 8 inherited autosomal recessive diseases characterized by the intralysosomal accumulation of autofluorescent pigments, called ceroids. Recent data suggest that the pathogenesis of NCLs is associated with the appearance of fragmented mitochondria with altered functions. However, even if an impairement in the ... More
Induction of heart valve lesions by small-molecule ALK5 inhibitors.
AuthorsAnderton MJ, Mellor HR, Bell A, Sadler C, Pass M, Powell S, Steele SJ, Roberts RR, Heier A,
JournalToxicol Pathol
PubMed ID21859884
Aberrant signaling by transforming growth factor-ß (TGF-ß) and its type I (ALK5) receptor has been implicated in a number of human diseases and this pathway is considered a potential target for therapeutic intervention. Transforming growth factor-ß signaling via ALK5 plays a critical role during heart development, but the role of ... 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
Real-time 2-photon imaging of mitochondrial function in perfused rat hearts subjected to ischemia/reperfusion.
AuthorsMatsumoto-Ida M, Akao M, Takeda T, Kato M, Kita T,
JournalCirculation
PubMed ID17000908
BACKGROUND: Mitochondria play pivotal roles in cell death; the loss of mitochondrial membrane potential (delta psi(m)) is the earliest event that commits the cell to death. Here, we report novel real-time imaging of delta psi(m) in individual cardiomyocytes within perfused rat hearts using 2-photon laser-scanning microscopy, which has unique advantages ... More
Bacterial programmed cell death of cerebral endothelial cells involves dual death pathways.
AuthorsBermpohl D, Halle A, Freyer D, Dagand E, Braun JS, Bechmann I, Schröder NW, Weber JR
JournalJ Clin Invest
PubMed ID15902310
Major barriers separating the blood from tissue compartments in the body are composed of endothelial cells. Interaction of bacteria with such barriers defines the course of invasive infections, and meningitis has served as a model system to study endothelial cell injury. Here we report the impressive ability of Streptococcus pneumoniae, ... More
Confocal restricted-height imaging of suspension cells (CRISC) in a PDMS microdevice during apoptosis.
AuthorsMuñoz-Pinedo C, Green DR, van den Berg A
JournalLab Chip
PubMed ID15915255
We have monitored and imaged cell death induced in human leukemic U937 cells over time using three-color confocal imaging. Three different apoptotic inducers, anti-Fas, TNF-alpha and Etoposide were used. Individual cascaded events such as loss of mitochondrial transmembrane potential, exposure of phosphatidyl-serine, membrane blebbing and permeabilization of the cell membrane ... More
Branched chain amino acids induce apoptosis in neural cells without mitochondrial membrane depolarization or cytochrome c release: implications for neurological impairment associated with maple syrup urine disease.
AuthorsJouvet P, Rustin P, Taylor DL, Pocock JM, Felderhoff-Mueser U, Mazarakis ND, Sarraf C, Joashi U, Kozma M, Greenwood K, Edwards AD, Mehmet H
JournalMol Biol Cell
PubMed ID10793161
Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by a deficiency in branched chain alpha-keto acid dehydrogenase that can result in neurodegenerative sequelae in human infants. In the present study, increased concentrations of MSUD metabolites, in particular alpha-keto isocaproic acid, specifically induced apoptosis in glial and ... More
Percolation and criticality in a mitochondrial network.
AuthorsAon MA, Cortassa S, O'Rourke B
JournalProc Natl Acad Sci U S A
PubMed ID15070738
Synchronization of mitochondrial function is an important determinant of cell physiology and survival, yet little is known about the mechanism of interorganellar communication. We have recently observed that coordinated cell-wide oscillations in the mitochondrial energy state of heart cells can be induced by a highly localized perturbation of a few ... More
Vaccinia virus encodes a previously uncharacterized mitochondrial-associated inhibitor of apoptosis.
AuthorsWasilenko ST, Stewart TL, Meyers AF, Barry M
JournalProc Natl Acad Sci U S A
PubMed ID14610284
To circumvent apoptotic death, many viruses encode Bcl-2 homologous proteins that function at the mitochondria. Vaccinia virus, the prototypic member of the Poxviridae family, does not encode a Bcl-2 homolog but inhibits the mitochondrial arm of the apoptotic cascade by an unknown mechanism. We now report that F1L, a previously ... More
Different mitochondrial intermembrane space proteins are released during apoptosis in a manner that is coordinately initiated but can vary in duration.
AuthorsMuñoz-Pinedo C, Guío-Carrión A, Goldstein JC, Fitzgerald P, Newmeyer DD, Green DR
JournalProc Natl Acad Sci U S A
PubMed ID16864784
The release of mitochondrial intermembrane space proteins to the cytosol is a key event during apoptosis. We used in situ fluorescent labeling of proteins tagged with a short tetracysteine-containing sequence to follow the release of Smac, Omi, adenylate kinase-2, cytochrome c, and apoptosis-inducing factor (AIF) during apoptosis and compared the ... More
Peripheral hot spots for local Ca2+ release after single action potentials in sympathetic ganglion neurons.
AuthorsCseresnyés Z, Schneider MF
JournalBiophys J
PubMed ID14695260
Ca2+ release from the endoplasmic reticulum (ER) contributes to Ca2+ transients in frog sympathetic ganglion neurons. Here we use video-rate confocal fluo-4 fluorescence imaging to show that single action potentials reproducibly trigger rapidly rising Ca2+ transients at 1-3 local hot spots within the peripheral ER-rich layer in intact neurons in ... More
Two-photon excitation imaging of pancreatic islets with various fluorescent probes.
AuthorsTakahashi N, Nemoto T, Kimura R, Tachikawa A, Miwa A, Okado H, Miyashita Y, Iino M, Kadowaki T, Kasai H
JournalDiabetes
PubMed ID11815453
Various fluorescent probes were assessed for investigating intact islets of Langerhans using two-photon excitation imaging. Polar fluorescent tracers applied on the outside rapidly (within 3 min) penetrated deep into the islets via microvessels. Likewise, an adenovirus carrying a Ca(2+)-sensitive green fluorescent protein mutant gene, yellow cameleon 2.1, was successfully transfected ... More
Microglial apoptosis induced by chromogranin A is mediated by mitochondrial depolarisation and the permeability transition but not by cytochrome c release.
AuthorsKingham PJ, Pocock JM
JournalJ Neurochem
PubMed ID10737601
Chromogranin A is up-regulated in the senile plaques of Alzheimer's brain and is a novel activator of microglia, transforming them to a neurotoxic phenotype. Treatment of primary cultures of rat brain microglia or the murine N9 microglial cell line with chromogranin A resulted in nitric oxide production, which triggered microglial ... More
Cytochrome c is released in a single step during apoptosis.
AuthorsGoldstein JC, Muñoz-Pinedo C, Ricci JE, Adams SR, Kelekar A, Schuler M, Tsien RY, Green DR
JournalCell Death Differ
PubMed ID15933725
Release of cytochrome c from mitochondria is a central event in apoptotic signaling. In this study, we utilized a cytochrome c fusion that binds fluorescent biarsenical ligands (cytochrome c-4CYS (cyt. c-4CYS)) as well as cytochrome c-green fluorescent protein (cyt. c-GFP) to measure its release from mitochondria in different cell types ... More
In vivo analysis of human multidrug resistance protein 1 (MRP1) activity using transient expression of fluorescently tagged MRP1.
AuthorsRajagopal A, Pant AC, Simon SM, Chen Y
JournalCancer Res
PubMed ID11809686
The multidrug resistance protein 1 (MRP1) contributes cellular resistance to a wide array of physiological toxins and chemotherapeutic agents. Its in vivo activity has been studied primarily in cells that have been continuously drug selected, culture conditions that might confound the effects of MRP1 expression with the effects of a ... More
Calcium influx through receptor-operated channel induces mitochondria-triggered paraptotic cell death.
AuthorsJambrina E, Alonso R, Alcalde M, del Carmen Rodríguez M, Serrano A, Martínez-A C, García-Sancho J, Izquierdo M
JournalJ Biol Chem
PubMed ID12571238
We address the specific role of cytoplasmic Ca(2+) overload as a cell death trigger by expressing a receptor-operated specific Ca(2+) channel, vanilloid receptor subtype 1 (VR1), in Jurkat cells. Ca(2+) uptake through the VR1 channel, but not capacitative Ca(2+) influx stimulated by the muscarinic type 1 receptor, induced sustained intracellular ... More
Nontranscriptional modulation of intracellular Ca2+ signaling by ligand stimulated thyroid hormone receptor.
AuthorsSaelim N, John LM, Wu J, Park JS, Bai Y, Camacho P, Lechleiter JD
JournalJ Cell Biol
PubMed ID15569710
Thyroid hormone 3,5,3'-tri-iodothyronine (T3) binds and activates thyroid hormone receptors (TRs). Here, we present evidence for a nontranscriptional regulation of Ca2+ signaling by T3-bound TRs. Treatment of Xenopus thyroid hormone receptor beta subtype A1 (xTRbetaA1) expressing oocytes with T3 for 10 min increased inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ wave periodicity. Coexpression ... More
Simultaneous imaging of cell and mitochondrial membrane potentials.
The distribution of charged membrane-permeable molecular probes between intracellular organelles, the cytoplasm, and the outside medium is governed by the relative membrane electrical potentials of these regions through coupled equilibria described by the Nernst equation. A series of highly fluorescent cationic dyes of low membrane binding and toxicity (Ehrenberg, B., ... More
Interferon alpha-induced apoptosis in tumor cells is mediated through the phosphoinositide 3-kinase/mammalian target of rapamycin signaling pathway.
AuthorsThyrell L, Hjortsberg L, Arulampalam V, Panaretakis T, Uhles S, Dagnell M, Zhivotovsky B, Leibiger I, Grandér D, Pokrovskaja K
JournalJ Biol Chem
PubMed ID15056668
Interferon (IFN) alpha induces a caspase-dependent apoptosis that is associated with activation of the proapoptotic Bak and Bax, loss of mitochondrial membrane potential, and release of cytochrome c. In addition to the onset of the classical Jak-STAT pathway, IFNalpha also induced phosphoinositide 3-kinase (PI3K) activity. Pharmacological inhibition of PI3K activity ... More
Mitochondrial permeability transition can be directly monitored in living neurons.
AuthorsGillessen T, Grasshoff C, Szinicz L
JournalBiomed Pharmacother
PubMed ID12109811
Mitochondria have been suggested as key players in apoptotic cell death of neurons and many other tissues, since the release of proapoptotic molecules from mitochondria is implicated in caspase activation. As a potential release mechanism, the occurrence of a large pore opening in the inner membrane (mitochondrial permeability transition pore, ... More
Bcl-xL inhibits cytochrome c release but not mitochondrial depolarization during the activation of multiple death pathways by tumor necrosis factor-alpha.
AuthorsJohnson BW, Cepero E, Boise LH
JournalJ Biol Chem
PubMed ID10913120
Cells can respond differently to anti-CD95 antibody treatment. Type I cells show strong activation of caspase-8 and directly activate caspase-3. Type II cells weakly activate caspase-8 and must amplify their death signal through the mitochondria. These cells can be rescued by Bcl-x(L). Here we show that tumor necrosis factor-alpha induces ... More
Long-chain fatty acids increase basal metabolism and depolarize mitochondria in cardiac muscle cells.
AuthorsRay J, Noll F, Daut J, Hanley PJ
JournalAm J Physiol Heart Circ Physiol
PubMed ID11893587
The effects of long-chain (LC) fatty acids on rate of heat production (heat rate) and mitochondrial membrane potential (DeltaPsi) of intact guinea pig cardiac muscle were investigated at 37 degrees C. Heat rate of ventricular trabeculae was measured with microcalorimetry, and DeltaPsi was monitored in isolated ventricular myocytes with either ... More
Caspase-dependent Cdk activity is a requisite effector of apoptotic death events.
AuthorsHarvey KJ, Lukovic D, Ucker DS
JournalJ Cell Biol
PubMed ID10629218
The caspase-dependent activation of cyclin-dependent kinases (Cdks) in varied cell types in response to disparate suicidal stimuli has prompted our examination of the role of Cdks in cell death. We have tested the functional role of Cdk activity in cell death genetically, with the expression of dominant negative Cdk mutants ... More
Characterization of visible dyes for four-decay fluorescence detection in DNA sequencing.
AuthorsNunnally BK, He H, Li LC, Tucker SA, McGown LB
JournalAnal Chem
PubMed ID9212706
Dyes of several classes were investigated as candidates for use in a multiplex, four-decay fluorescence detection scheme for DNA sequencing. The dyes include nitrobenzofuran dyes, rhodamine dyes, fluorescein dyes, cyanine dyes, Nile Red, and BODIPY dyes. Based on the results of fluorescence spectral and lifetime studies, an initial set of ... More
Full-length p73alpha represses drug-induced apoptosis in small cell lung carcinoma cells.
AuthorsNyman U, Sobczak-Pluta A, Vlachos P, Perlmann T, Zhivotovsky B, Joseph B
JournalJ Biol Chem
PubMed ID16087678
The p73 gene, a member of the p53 family, encodes several variants through differential splicing and use of alternative promoters. At the NH2 terminus, two different promoters generate the full-length and the DeltaN isoforms, with or without the transactivating domain. At the COOH terminus, seven isoforms generated through alternative splicing ... More
Loss of OPA1 perturbates the mitochondrial inner membrane structure and integrity, leading to cytochrome c release and apoptosis.
AuthorsOlichon A, Baricault L, Gas N, Guillou E, Valette A, Belenguer P, Lenaers G
JournalJ Biol Chem
PubMed ID12509422
OPA1 encodes a large GTPase related to dynamins, anchored to the mitochondrial cristae inner membrane, facing the intermembrane space. OPA1 haplo-insufficiency is responsible for the most common form of autosomal dominant optic atrophy (ADOA, MIM165500), a neuropathy resulting from degeneration of the retinal ganglion cells and optic nerve atrophy. Here ... More
Membrane potential can be determined in individual cells from the nernstian distribution of cationic dyes.
The distribution of a selection of cationic fluorescent dyes can be used to measure the membrane potential of individual cells with a microfluorometer. The essential attributes of these dyes include membrane permeability, low membrane binding, spectral properties which are insensitive to environment, and, of course, strong fluorescence. A series of ... More
Critical role for DP5/Harakiri, a Bcl-2 homology domain 3-only Bcl-2 family member, in axotomy-induced neuronal cell death.
AuthorsImaizumi K, Benito A, Kiryu-Seo S, Gonzalez V, Inohara N, Lieberman AP, Kiyama H, Nuñez G, Leiberman AP
JournalJ Neurosci
PubMed ID15084651
The survival of neurons is maintained primarily by neurotrophic factors that suppress the apoptotic program. Axotomy or removal of peripheral targets causes neuronal cell death, but the mechanisms involved in the induction of this type of cell death remain poorly understood. Here, we show that DP5/Harakiri, a Bcl-2 homology domain ... More
Dual-targeting immunotherapy of lymphoma: potent cytotoxicity of anti-CD20/CD74 bispecific antibodies in mantle cell and other lymphomas.
We describe the use of novel bispecific hexavalent Abs (HexAbs) to enhance anticancer immunotherapy. Two bispecific HexAbs [IgG-(Fab)(4) constructed from veltuzumab (anti-CD20 IgG) and milatuzumab (anti-CD74 IgG)] show enhanced cytotoxicity in mantle cell lymphoma (MCL) and other lymphoma/leukemia cell lines, as well as patient tumor samples, without a crosslinking Ab, ... More
Hibernation during hypoxia in cardiomyocytes. Role of mitochondria as the O2 sensor.
During myocardial hibernation, decreases in coronary perfusion elicit inhibition of contraction, suggesting that energy demand is attenuated. We previously found an inhibition of contraction and O2 consumption during hypoxia (3% O2; PO2 = 20 torr for >2 h) in cardiomyocytes, which was reversible after reoxygenation. This study sought to determine ... More
Contributions of mitochondria to animal physiology: from homeostatic sensor to calcium signalling and cell death.
AuthorsDuchen MR
JournalJ Physiol
PubMed ID10066918
Over recent years, it has become clear that mitochondria play a central role in many key aspects of animal physiology and pathophysiology. Their central and ubiquitous task is clearly the production of ATP. Nevertheless, they also play subtle roles in glucose homeostasis, acting as the sensor for substrate supply in ... More
Mitochondria are morphologically and functionally heterogeneous within cells.
AuthorsCollins TJ, Berridge MJ, Lipp P, Bootman MD
JournalEMBO J
PubMed ID11927546
We investigated whether mitochondria represent morphologically continuous and functionally homogenous entities within single intact cells. Physical continuity of mitochondria was determined by three-dimensional reconstruction of fluorescence from mitochondrially targeted DsRed1 or calcein. The mitochondria of HeLa, PAEC, COS-7, HUVEC, hepatocytes, cortical astrocytes and neuronal cells all displayed heterogeneous distributions and ... More
Simvastatin attenuates oxidant-induced mitochondrial dysfunction in cardiac myocytes.
AuthorsJones SP, Teshima Y, Akao M, Marbán E
JournalCirc Res
PubMed ID14512440
3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) can exert beneficial effects independently of serum cholesterol reduction by increasing the bioavailability of nitric oxide. However, it is unclear whether statins can exert such effects directly on cardiac myocytes and whether mitochondria are potential targets. Neonatal rat cardiac myocytes were cultured and subjected ... More
Imaging the permeability pore transition in single mitochondria.
AuthorsHüser J, Rechenmacher CE, Blatter LA
JournalBiophys J
PubMed ID9545072
In mitochondria the opening of a large proteinaceous pore, the "mitochondrial permeability transition pore" (MTP), is known to occur under conditions of oxidative stress and matrix calcium overload. MTP opening and the resulting cellular energy deprivation have been implicated in processes such as hypoxic cell damage, apoptosis, and neuronal excitotoxicity. ... More
Ligand-induced trafficking of the sphingosine-1-phosphate receptor EDG-1.
AuthorsLiu CH, Thangada S, Lee MJ, Van Brocklyn JR, Spiegel S, Hla T
JournalMol Biol Cell
PubMed ID10198065
The endothelial-derived G-protein-coupled receptor EDG-1 is a high-affinity receptor for the bioactive lipid mediator sphingosine-1-phosphate (SPP). In the present study, we constructed the EDG-1-green fluorescent protein (GFP) chimera to examine the dynamics and subcellular localization of SPP-EDG-1 interaction. SPP binds to EDG-1-GFP and transduces intracellular signals in a manner indistinguishable ... More
Elevation of resting mitochondrial membrane potential of neural cells by cyclosporin A, BAPTA-AM, and bcl-2.
AuthorsKowaltowski AJ, Smaili SS, Russell JT, Fiskum G
JournalAm J Physiol Cell Physiol
PubMed ID10942734
This study tested the hypothesis that the activity of the mitochondrial membrane permeability transition pore (PTP) affects the resting mitochondrial membrane potential (DeltaPsi) of normal, healthy cells and that the anti-apoptotic gene product Bcl-2 inhibits the basal activity of the PTP. DeltaPsi was measured by both fluorometric and nonfluorometric methods ... More