Research Topics
Genomes and Genes | Sten OrreniusSummaryAffiliation: Karolinska Institutet Country: Sweden Publications
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Publications
Mitochondrial oxidative stress: implications for cell deathSten Orrenius
Institute of Environmental Medicine, Karolinska Institutet, S 171 77 Stockholm, Sweden
Annu Rev Pharmacol Toxicol 47:143-83. 2007..Taken together, these findings have placed the mitochondria in the focus of current cell death research...- Mitochondria, oxidative stress and cell deathMartin Ott
Institute of Environmental Medicine, Karolinska Institutet, S 171 77 Stockholm, Sweden
Apoptosis 12:913-22. 2007..Conversely, mitochondrial antioxidant enzymes protect from apoptosis. Hence, there is accumulating evidence supporting a direct link between mitochondria, oxidative stress and cell death... 
Autophagy in toxicology: cause or consequence?Sten Orrenius
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, SE 17177 Stockholm, Sweden
Annu Rev Pharmacol Toxicol 53:275-97. 2013..However, the relative contribution of autophagy to the overall toxicity of these compounds is not always clear, and further research is needed to clarify the toxicological significance of this process...- Reactive oxygen species in mitochondria-mediated cell deathSten Orrenius
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
Drug Metab Rev 39:443-55. 2007..Taken together, these findings have placed the mitochondria in the focus of current cell death research... - Cell death mechanisms and their implications in toxicologySten Orrenius
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, SE 171 77 Stockholm, Sweden
Toxicol Sci 119:3-19. 2011..Hence, the cell death and phagocytosis regulatory networks offer a multitude of targets for toxic chemicals... - The future of toxicology--does it matter how cells die?Sten Orrenius
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Stockholm, Sweden
Chem Res Toxicol 19:729-33. 2006 - Early work on apoptosis, an interview with Sten OrreniusSten Orrenius
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden
Cell Death Differ 13:1-4. 2006 - Differential regulation of the mitochondrial and death receptor pathways in neural stem cellsChristoffer Tamm
Institute of Environmental Medicine, Division of Toxicology and Neurotoxicology, Karolinska Institutet, 71 77 Stockholm, Sweden
Eur J Neurosci 19:2613-21. 2004..Combined, our findings indicate that while NSCs are sensitive to cytotoxic stimuli that involve an engagement of mitochondria, Fas treatment does not induce death and may have an alternative role... 
Processed caspase-2 can induce mitochondria-mediated apoptosis independently of its enzymatic activityJohn D Robertson
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden
EMBO Rep 5:643-8. 2004..Combined, our data suggest that caspase-2 retains a unique ability to engage directly the mitochondrial apoptotic pathway, an effect that requires processing of the zymogen but not the associated catalytic activity...- Analysis of mitochondrial dysfunction during cell deathVladimir Gogvadze
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
Curr Protoc Cell Biol . 2003.... - Involvement of Ca2+ and ROS in alpha-tocopheryl succinate-induced mitochondrial permeabilizationVladimir Gogvadze
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
Int J Cancer 127:1823-32. 2010..Importantly, Ca(2+)-induced mitochondrial destabilization might cooperate with Bax-mediated mitochondrial outer membrane permeabilization to induce cytochrome c release from mitochondria... - Phosphatidylserine exposure in Fas type I cells is mitochondria-dependentWanlaya Uthaisang
Institute of Environmental Medicine, Division of Toxicology, , Karolinska Institutet, 171 77, Stockholm, Sweden
FEBS Lett 545:110-4. 2003..These studies thus demonstrate that PS externalization and clearance of cell corpses are mitochondria-dependent events, and show that these events can be dissociated from other features of the apoptotic program, in Fas type I cells... - Plasma membrane sequestration of apoptotic protease-activating factor-1 in human B-lymphoma cells: a novel mechanism of chemoresistanceYu Sun
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
Blood 105:4070-7. 2005..Together, our findings suggest that ectopic (noncytosolic) localization of Apaf-1 may constitute a novel mechanism of chemoresistance in B lymphoma... - Mitochondria as targets for cancer chemotherapyVladimir Gogvadze
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
Semin Cancer Biol 19:57-66. 2009..This review is devoted to the role of mitochondria in cell death, and describes how targeting of mitochondria can make tumor cells more susceptible to anticancer treatment... - Cardiolipin is not required for Bax-mediated cytochrome c release from yeast mitochondriaSuzanne L Iverson
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden
J Biol Chem 279:1100-7. 2004..In contrast, they support our recently proposed two-step mechanism of cytochrome c release, which suggests that CL is required for binding cytochrome c to the inner mitochondrial membrane... - Caspase-2 permeabilizes the outer mitochondrial membrane and disrupts the binding of cytochrome c to anionic phospholipidsMari Enoksson
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden
J Biol Chem 279:49575-8. 2004.... - Indirect effects of Bax and Bak initiate the mitochondrial alterations that lead to cytochrome c release during arsenic trioxide-induced apoptosisLeta K Nutt
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Stockholm, Sweden
Cancer Biol Ther 4:459-67. 2005..Furthermore, the results implicate reactive oxygen species in a concentration-dependent mechanistic switch between apoptosis and necrosis... - Critical role for hyperpolarization-activated cyclic nucleotide-gated channel 2 in the AIF-mediated apoptosisErik Norberg
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
EMBO J 29:3869-78. 2010..Our findings demonstrate a novel role for the HCN2 channel by providing evidence that it can act as an upstream regulator of cell death triggered by PKC inhibitors... - Overexpression of glutaredoxin 2 attenuates apoptosis by preventing cytochrome c releaseMari Enoksson
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, SE 171 77 Stockholm, Sweden
Biochem Biophys Res Commun 327:774-9. 2005..We propose that Grx2 facilitates the maintenance of cellular redox homeostasis upon treatment with apoptotic agents, thereby preventing cardiolipin oxidation and cytochrome c release... - Mitochondrial cytochrome c release may occur by volume-dependent mechanisms not involving permeability transitionVladimir Gogvadze
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden
Biochem J 378:213-7. 2004..In contrast with mitochondrial permeability transition-dependent release of cytochrome c, in the present study mitochondria remain intact and functionally active... - Oxidative modification sensitizes mitochondrial apoptosis-inducing factor to calpain-mediated processingErik Norberg
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, SE 171 77 Stockholm, Sweden
Free Radic Biol Med 48:791-7. 2010..Combined, our data provide evidence that ROS-mediated, posttranslational modification of AIF is critical for its cleavage by calpain and thus for AIF-mediated cell death... - Citrate kills tumor cells through activation of apical caspasesBjörn Kruspig
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden
Cell Mol Life Sci 69:4229-37. 2012..Caspase-8 is activated by proximity-induced dimerization, which might be facilitated by citrate through the stabilization of intermolecular interactions between the proteins... - Calcium and cell death mechanisms: a perspective from the cell death communityBoris Zhivotovsky
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, SE 171 77 Stockholm, Sweden
Cell Calcium 50:211-21. 2011..Characteristics, interrelationship and mechanisms involved in Ca(2+) regulation of these cell death modalities are discussed in this review... - Multiple pathways of cytochrome c release from mitochondria in apoptosisVladimir Gogvadze
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box-210, SE-171 77, Stockholm, Sweden
Biochim Biophys Acta 1757:639-47. 2006..The variety of mechanisms that can lead to outer membrane permeabilization might explain diversities in the response of mitochondria to numerous apoptotic stimuli in different types of cells... - Mitochondria in cancer cells: what is so special about them?Vladimir Gogvadze
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, Stockholm, SE 171 77, Sweden
Trends Cell Biol 18:165-73. 2008.... - The mitochondrial TOM complex is required for tBid/Bax-induced cytochrome c releaseMartin Ott
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, SE 171 77 Stockholm, Sweden
J Biol Chem 282:27633-9. 2007..Here, we show that the protein translocase of the outer mitochondrial membrane is required for Bax insertion and cytochrome c release... - Mitochondria as targets for chemotherapyVladimir Gogvadze
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
Apoptosis 14:624-40. 2009..This review is devoted to the role of mitochondria in neurodegeneration and tumor formation, and describes how targeting of mitochondria can be beneficial in the therapy of these diseases, which affect a large human population... - Regulation of cell death: the calcium-apoptosis linkSten Orrenius
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, SE 171 77 Stockholm, Sweden
Nat Rev Mol Cell Biol 4:552-65. 2003..However, more recently it has become clear that cellular Ca2+ overload, or perturbation of intracellular Ca2+ compartmentalization, can cause cytotoxicity and trigger either apoptotic or necrotic cell death... - Caspase-2 acts upstream of mitochondria to promote cytochrome c release during etoposide-induced apoptosisJohn D Robertson
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE 171 77 Stockholm, Sweden
J Biol Chem 277:29803-9. 2002..Taken together, our data indicate that caspase-2 provides an important link between etoposide-induced DNA damage and the engagement of the mitochondrial apoptotic pathway... - The Warburg effect and mitochondrial stability in cancer cellsVladimir Gogvadze
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, Stockholm SE 17177, Sweden
Mol Aspects Med 31:60-74. 2010.... - Targeting mitochondria by α-tocopheryl succinate kills neuroblastoma cells irrespective of MycN oncogene expressionBjörn Kruspig
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
Cell Mol Life Sci 69:2091-9. 2012..Prevention of mitochondrial Ca(2+) accumulation or chelation of cytosolic Ca(2+) rescued the cells. Thus, targeting mitochondria might be advantageous for the elimination of tumor cells with otherwise dormant apoptotic pathways... - The cardiolipin-cytochrome c interaction and the mitochondrial regulation of apoptosisSuzanne L Iverson
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Stockholm, Sweden
Arch Biochem Biophys 423:37-46. 2004..In this review, we discuss the significance of the disruption of the CL-cytochrome c interaction for cytochrome c release and apoptosis... - Caspase-2 function in response to DNA damageBoris Zhivotovsky
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, SE 171 77 Stockholm, Sweden
Biochem Biophys Res Commun 331:859-67. 2005..In this review, current knowledge concerning the structure of this protease and its function in cell physiology and cell death, particularly cell death triggered by DNA damage, is summarized and discussed... - Mitochondrial regulation of cell death: processing of apoptosis-inducing factor (AIF)Erik Norberg
Institute of Environmental Medicine, Division of Toxicology Karolinska Institutet, SE 17177 Stockholm, Sweden
Biochem Biophys Res Commun 396:95-100. 2010..The current knowledge about the molecular mechanisms regulating the processing and release of AIF from the mitochondria will be summarized and discussed in this review... - Tributyltin causes cytochrome C release from isolated mitochondria by two discrete mechanismsVladimir Gogvadze
Division of Toxicology, Institute of Environmental Medicine, Stockholm, SE-171-77, Sweden
Biochem Biophys Res Commun 292:904-8. 2002..Gigliotti, D., Orrenius, S., and Cotgreave, I. A. (1999) Biochem. Biophys. Res. Commun. 266, 460-465)... - Role of mitochondria in toxic cell deathJohn D Robertson
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden
Toxicology 181:491-6. 2002.... - Mitochondrial regulation of apoptotic cell deathSten Orrenius
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, SE 171 77 Stockholm, Sweden
Toxicol Lett 149:19-23. 2004..Taken together, these findings have placed the mitochondria in the focus of apoptosis research and further underlined the important function of these organelles in cell life and death... - Cytochrome c release from mitochondria proceeds by a two-step processMartin Ott
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE 171 77 Stockholm, Sweden
Proc Natl Acad Sci U S A 99:1259-63. 2002..Our results indicate that the release of cytochrome c involves a distinct two-step process that is undermined when either step is compromised... - Buried alive: a novel approach to cancer treatmentBengt Fadeel
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Stockholm, Sweden
FASEB J 18:1-4. 2004..In other words, inducing the expression of "eat me" signals on cancer cells could be a novel approach to "bury alive" these unwanted cells without the untoward effects of chemotherapy-induced apoptosis... - Reactive oxygen species generated in different compartments induce cell death, survival, or senescenceEmiliano Panieri
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, SE 171 77 Stockholm, Sweden
Free Radic Biol Med 57:176-87. 2013..Combined, our data provide evidence that ROS might dictate different cellular consequences depending on their overall concentration at steady-state levels and on their site of generation... - Defects in the apoptotic machinery of cancer cells: role in drug resistanceBoris Zhivotovsky
Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE 171 77 Stockholm, Sweden
Semin Cancer Biol 13:125-34. 2003..Here we review known differences in the apoptotic machinery in cancer cells, and how this knowledge can be used to increase the efficiency of tumor treatment... - Carcinogenesis and apoptosis: paradigms and paradoxesBoris Zhivotovsky
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet Box 210, SE 171 77 Stockholm, Sweden
Carcinogenesis 27:1939-45. 2006..However, the precise role of these genes and their products in cancer development is less clear. Here, we will discuss some of the current paradigms and paradoxes concerning the involvement of apoptotic genes in carcinogenesis... - Evaluation of caspase activity in apoptotic cellsCamilla Köhler
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE 171 77 Stockholm, Sweden
J Immunol Methods 265:97-110. 2002..Each method is described in general terms and the advantages and disadvantages of each technique are discussed... - Fas-triggered phosphatidylserine exposure is modulated by intracellular ATPBettina Gleiss
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Stockholm, Sweden
FEBS Lett 519:153-8. 2002..These studies suggest that intracellular ATP levels can modulate the externalization of PS during apoptosis, and implicate the ATP-dependent aminophospholipid translocase in this process... - Resistance of leukemic cells to 2-chlorodeoxyadenosine is due to a lack of calcium-dependent cytochrome c releaseJoya Chandra
Institute for Environmental Medicine, Division of Toxicology, and Department of Medicine, Karolinska Institutet, Stockholm, Sweden
Blood 99:655-63. 2002..Taken together, the data indicate that the mechanism of resistance to CdA may be dictated by changes in Ca2+-sensitive mitochondrial events... - Mitochondrial regulation of apoptotic cell deathVladimir Gogvadze
Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden
Chem Biol Interact 163:4-14. 2006..The multiple mechanisms of mitochondrial permeabilization may explain diversities in the response of mitochondria to numerous apoptotic stimuli in different types of cells... - Cell death mechanisms: cross-talk and role in diseaseBoris Zhivotovsky
Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE 171 77 Stockholm, Sweden
Exp Cell Res 316:1374-83. 2010..In this review we shall discuss the characteristics and cross-talk between various modes of cell death and their role in cell death-related disorders, notably, neurodegenerative disease and cancer... - [Sydney Brenner, Robert Horvitz and John Sulston. Winners of the 2002 Nobel Prize in medicine or physiology. Genetic regulation of organ development and programmed cell death]Urban Lendahl
, Karolinska Institutet, Stockholm
Lakartidningen 99:4026-32. 2002 - A role for oxidative stress in apoptosis: oxidation and externalization of phosphatidylserine is required for macrophage clearance of cells undergoing Fas-mediated apoptosisValerian E Kagan
Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260, USA
J Immunol 169:487-99. 2002..Taken together, our data suggest that the presence of PS-OX in conjunction with nonoxidized PS on the cell surface is an important signal for macrophage clearance of apoptotic cells... - Cardiolipin oxidation sets cytochrome c freeSten Orrenius
Nat Chem Biol 1:188-9. 2005 - Role of mitochondria in toxic oxidative stressMarc W Fariss
Department of Pharmaceutical Sciences, University of Colorado Cancer Center, Denver, CO 80262, USA
Mol Interv 5:94-111. 2005.... - Arsenic stimulates release of cytochrome c from isolated mitochondria via induction of mitochondrial permeability transitionJuanita Bustamante
Department of Physical Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina
Toxicol Appl Pharmacol 207:110-6. 2005.... - HAMLET, protein folding, and tumor cell deathK Hun Mok
Trinity College, School of Biochemistry and Immunology, University of Dublin, Dublin 2, Ireland
Biochem Biophys Res Commun 354:1-7. 2007 - Phosphatidylserine externalization in cardiolipin-deficient cellsBengt Fadeel
Blood 104:1582-3; author reply 1583-4. 2004 - Visualization of the compartmentalization of glutathione and protein-glutathione mixed disulfides in cultured cellsTherese Söderdahl
Division of Biochemical Toxicology, Karolinska Institutet, Stockholm Sweden
FASEB J 17:124-6. 2003..Similar FACS analyses performed in isolated mitochondria presented a considerable variation in GSH content within mitochondria of uniform granularity from the same preparation...