Standardized mitochondrial analysis gives new insights into mitochondrial dynamics and OPA1 function.
AuthorsChevrollier A, Cassereau J, Ferré M, Alban J, Desquiret-Dumas V, Gueguen N, Amati-Bonneau P, Procaccio V, Bonneau D, Reynier P,
JournalInt J Biochem Cell Biol
PubMed ID22433900
'Mitochondria form dynamic tubular networks through processes of fission and fusion. Defect in mitochondrial dynamics lead to various pathologies, including several common and some rare neurodegenerative disorders. OPA1 and MFN2 are two key players in mitochondrial fusion associated with Autosomal Dominant Optic Atrophy and Charcot Marie Tooth neuropathy type 2A ... 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
Energy metabolism in human pluripotent stem cells and their differentiated counterparts.
AuthorsVarum S, Rodrigues AS, Moura MB, Momcilovic O, Easley CA, Ramalho-Santos J, Van Houten B, Schatten G,
JournalPLoS One
PubMed ID21698063
'BACKGROUND: Human pluripotent stem cells have the ability to generate all cell types present in the adult organism, therefore harboring great potential for the in vitro study of differentiation and for the development of cell-based therapies. Nonetheless their use may prove challenging as incomplete differentiation of these cells might lead ... More
Nitrite activates protein kinase A in normoxia to mediate mitochondrial fusion and tolerance to ischaemia/reperfusion.
'Nitrite (NO2(-)), a dietary constituent and nitric oxide (NO) oxidation product, mediates cardioprotection after ischaemia/reperfusion (I/R) in a number of animal models when administered during ischaemia or as a pre-conditioning agent hours to days prior to the ischaemic episode. When present during ischaemia, the reduction of nitrite to bioactive NO ... More
Inhibition of AMP-activated protein kinase a (AMPKa) by doxorubicin accentuates genotoxic stress and cell death in mouse embryonic fibroblasts and cardiomyocytes: role of p53 and SIRT1.
AuthorsWang S, Song P, Zou MH,
JournalJ Biol Chem
PubMed ID22267730
'Doxorubicin, an anthracycline antibiotic, is widely used in cancer treatment. Doxorubicin produces genotoxic stress and p53 activation in both carcinoma and non-carcinoma cells. Although its side effects in non-carcinoma cells, especially in heart tissue, are well known, the molecular targets of doxorubicin are poorly characterized. Here, we report that doxorubicin ... More
Life cell quantification of mitochondrial membrane potential at the single organelle level.
AuthorsDistelmaier F, Koopman WJ, Testa ER, de Jong AS, Swarts HG, Mayatepek E, Smeitink JA, Willems PH,
JournalCytometry A
PubMed ID18163486
'Mitochondrial membrane potential (Deltapsi) is key to mitochondrial function and cellular survival. Here, we aimed to develop an automated protocol allowing sensitive quantification of Deltapsi in living cells at the level of individual mitochondria. Human skin fibroblasts were stained with the fluorescent cation tetramethyl rhodamine methyl ester (TMRM), which is ... More
Mitochondrial dynamics and motility inside living vascular endothelial cells: role of bioenergetics.
AuthorsGiedt RJ, Pfeiffer DR, Matzavinos A, Kao CY, Alevriadou BR,
JournalAnn Biomed Eng
PubMed ID22527011
'The mitochondrial network is dynamic with conformations that vary between a tubular continuum and a fragmented state. The equilibrium between mitochondrial fusion/fission, as well as the organelle motility, determine network morphology and ultimately mitochondrial/cell function. Network morphology has been linked with the energy state in different cell types. In this ... More
Distinct roles of mitochondria- and ER-localized Bcl-xL in apoptosis resistance and Ca2+ homeostasis.
AuthorsEno CO, Eckenrode EF, Olberding KE, Zhao G, White C, Li C,
JournalMol Biol Cell
PubMed ID22573883
Bcl-2 proteins are major regulators of cellular responses to intrinsic and extrinsic apoptotic stimuli. Among them, overexpression of the antiapoptotic protein Bcl-x(L) modulates intracellular Ca(2+) homeostasis and organelle-specific apoptotic signaling pathways. However, the specific activities of Bcl-x(L) at mitochondria and the endoplasmic reticulum (ER) have not been fully defined. To ... More
The mitochondrial protein C1qbp promotes cell proliferation, migration and resistance to cell death.
AuthorsMcGee AM, Douglas DL, Liang Y, Hyder SM, Baines CP,
JournalCell Cycle
PubMed ID22101277
Complement 1q-Binding Protein (C1qbp) is a mitochondrial protein reported to be upregulated in cancer. However, whether C1qbp plays a tumor suppressive or tumorigenic role in the progression of cancer is controversial. Moreover, the exact effects of C1qbp on cell proliferation, migration, and death/survival have not been definitely proven. To this ... More
Hemin causes mitochondrial dysfunction in endothelial cells through promoting lipid peroxidation: the protective role of autophagy.
AuthorsHigdon AN, Benavides GA, Chacko BK, Ouyang X, Johnson MS, Landar A, Zhang J, Darley-Usmar VM,
JournalAm J Physiol Heart Circ Physiol
PubMed ID22245770
The hemolysis of red blood cells and muscle damage results in the release of the heme proteins myoglobin, hemoglobin, and free heme into the vasculature. The mechanisms of heme toxicity are not clear but may involve lipid peroxidation, which we hypothesized would result in mitochondrial damage in endothelial cells. To ... More
Identifying and localizing intracellular nanoparticles using Raman spectroscopy.
AuthorsDorney J, Bonnier F, Garcia A, Casey A, Chambers G, Byrne HJ,
JournalAnalyst
PubMed ID22273712
Raman microscopy is employed to spectroscopically image biological cells previously exposed to fluorescently labelled polystyrene nanoparticles and, in combination with K-means clustering and principal component analysis (PCA), is demonstrated to be capable of localising the nanoparticles and identifying the subcellular environment based on the molecular spectroscopic signatures. The neutral nanoparticles ... More
Apoptosis-inducing factor (AIF) is targeted in IFN-a2a-induced Bid-mediated apoptosis through Bak activation in ovarian cancer cells.
AuthorsMiyake K, Bekisz J, Zhao T, Clark CR, Zoon KC,
JournalBiochim Biophys Acta
PubMed ID22683989
Previously we have shown that interferon (IFN)-a induced apoptosis is predominantly mediated by the upregulation of tumor necrosis factor related apoptosis-inducing ligand (TRAIL) via the caspase-8 pathway. It was also shown that recruitment of mitochondria in IFN-a induced apoptosis involves the cleavage of BH3 interacting domain death agonist (Bid) to ... More
Baculovirus-mediated gene transfer into mammalian cells.
AuthorsBoyce FM, Bucher NL,
JournalProc Natl Acad Sci U S A
PubMed ID8637876
This paper describes the use of the baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) as a vector for gene delivery into mammalian cells. A modified AcMNPV virus was prepared that carried the Escherichia coli lacZ reporter gene under control of the Rous sarcoma virus promoter and mammalian RNA processing ... More
BacMam technology and its application to drug discovery.
AuthorsAmes RS, Kost TA, Condreay JP,
JournalExpert Opin Drug Discov
PubMed ID23488908
The recombinant baculovirus/insect cell system was firmly established as a leading method for recombinant protein production when a new potential use for these viruses was revealed in 1995. It was reported that engineered recombinant baculoviruses could deliver functional expression cassettes to mammalian cell types; a system which has come to ... More
Dynamin-related protein 1 (Drp1)-mediated diastolic dysfunction in myocardial ischemia-reperfusion injury: therapeutic benefits of Drp1 inhibition to reduce mitochondrial fission.
AuthorsSharp WW, Fang YH, Han M, Zhang HJ, Hong Z, Banathy A, Morrow E, Ryan JJ, Archer SL,
Journal
PubMed ID24076965
Mitochondrial fission, regulated by dynamin-related protein-1 (Drp1), is a newly recognized determinant of mitochondrial function, but its contribution to left ventricular (LV) impairment following ischemia-reperfusion (IR) injury is unknown. We report that Drp1 activation during IR results in LV dysfunction and that Drp1 inhibition is beneficial. In both isolated neonatal ... More
Chain length of saturated fatty acids regulates mitochondrial trafficking and function in sensory neurons.
'Dyslipidemia associated with T2D leads to diabetic neuropathy, a complication characterized by sensory neuronal dysfunction and peripheral nerve damage. Sensory dorsal root ganglion (DRG) neurons are dependent on axonal mitochondrial energy production facilitated by mitochondrial transport mechanisms that distribute mitochondria throughout the axon. Because long-chain saturated FAs (SFAs) damage DRG ... More
The iron chelator Deferasirox causes severe mitochondrial swelling without depolarization due to a specific effect on inner membrane permeability.
AuthorsGottwald EM, Schuh CD, Drücker P, Haenni D, Pearson A, Ghazi S, Bugarski M, Polesel M, Duss M, Landau EM, Kaech A, Ziegler U, Lundby AKM, Lundby C, Dittrich PS, Hall AM
JournalSci Rep
PubMed ID32005861
'The iron chelator Deferasirox (DFX) causes severe toxicity in patients for reasons that were previously unexplained. Here, using the kidney as a clinically relevant in vivo model for toxicity together with a broad range of experimental techniques, including live cell imaging and in vitro biophysical models, we show that DFX ... More
Traumatic brain injury in the presence of Aβ pathology affects neuronal survival, glial activation and autophagy.
Authors
JournalSci Rep
PubMed ID34837024
PU-91 drug rescues human age-related macular degeneration RPE cells; implications for AMD therapeutics.
Authors
JournalAging (Albany NY)
PubMed ID31477635
Impaired mitophagy leads to cigarette smoke stress-induced cellular senescence: implications for chronic obstructive pulmonary disease.
Authors
JournalFASEB J
PubMed ID25792665
Effects of O-GlcNAcylation on functional mitochondrial transfer from astrocytes.
Authors
JournalJ Cereb Blood Flow Metab
PubMed ID33153373
Detection of large extracellular silver nanoparticle rings observed during mitosis using darkfield microscopy.
Authors
JournalPLoS One
PubMed ID33259485
Characterizing the protective effects of SHLP2, a mitochondrial-derived peptide, in macular degeneration.
Endoplasmic Reticulum Interaction Supports Energy Production and Redox Homeostasis in Mitochondria Released from Astrocytes.
Authors
JournalTransl Stroke Res
PubMed ID33479917
Human mesenchymal stromal cells transplanted into mice stimulate renal tubular cells and enhance mitochondrial function.
Authors
JournalNat Commun
PubMed ID29042548
Transit and integration of extracellular mitochondria in human heart cells.
Authors
JournalSci Rep
PubMed ID29234096
BID and the a-bisabolol-triggered cell death program: converging on mitochondria and lysosomes.
AuthorsRigo A, Ferrarini I, Lorenzetto E, Darra E, Liparulo I, Bergamini C, Sissa C, Cavalieri E, Vinante F
JournalCell Death Dis
PubMed ID31767857
a-Bisabolol (BSB) is a plant-derived sesquiterpene alcohol able to trigger regulated cell death in transformed cells, while deprived of the general toxicity in several mouse models. Here, we investigated the involvement of lysosomal and mitochondrial compartments in the cytotoxic effects of BSB, with a specific focus on the BH3-only activator ... More
Optimizing beta cell function through mesenchymal stromal cell-mediated mitochondria transfer.
AuthorsRackham CL, Hubber EL, Czajka A, Malik AN, King AJF, Jones PM
JournalStem Cells
PubMed ID31912945
Pretransplant islet culture is associated with the loss of islet cell mass and insulin secretory function. Insulin secretion from islet ß-cells is primarily controlled by mitochondrial ATP generation in response to elevations in extracellular glucose. Coculture of islets with mesenchymal stromal cells (MSCs) improves islet insulin secretory function in vitro, ... More
Therapeutic use of extracellular mitochondria in CNS injury and disease.
AuthorsNakamura Y, Park JH, Hayakawa K
JournalExp Neurol
PubMed ID31734316
In the central nervous system (CNS), neuronal functionality is highly dependent on mitochondrial integrity and activity. In the context of a damaged or diseased brain, mitochondrial dysfunction leads to reductions in ATP levels, thus impairing ATP-dependent neural firing and neurotransmitter dynamics. Restoring mitochondrial ability to generate ATP may be a ... More