The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Craig B Thompson - One of the best experts on this subject based on the ideXlab platform.
-
Mitochondrial Membrane potential regulates matrix configuration and cytochrome c release during apoptosis
Cell Death & Differentiation, 2003Co-Authors: Eyal Gottlieb, Marian H Harris, Sean M Armour, Craig B ThompsonAbstract:Mitochondrial Membrane potential regulates matrix configuration and cytochrome c release during apoptosis
-
bcl x l promotes the open configuration of the voltage dependent anion channel and metabolite passage through the outer Mitochondrial Membrane
Journal of Biological Chemistry, 2001Co-Authors: Matthew Vander G Heiden, Xiao Xian Li, Craig B Thompson, E Gottleib, Blake R Hill, Marco ColombiniAbstract:Abstract The diffusion of metabolites across the outer Mitochondrial Membrane is essential for coupled cellular respiration. The outer Membrane of mitochondria isolated from growth factor-deprived cells is impaired in its ability to exchange metabolic anions. When added to mitochondria, recombinant Bcl-xL restores metabolite exchange across the outer Membrane without inducing the loss of cytochrome c from the interMembrane space. Restoration of outer Membrane permeability to anionic metabolites does not occur directly through Bcl-xLion channels. Instead, recombinant Bcl-xL maintains the outer Mitochondrial Membrane channel, VDAC, in an open configuration. Consistent with these findings, when ADP-induced oxidative phosphorylation is limited by exogenous β-NADH, recombinant Bcl-xL can sustain outer Mitochondrial Membrane permeability to ADP. β-NADH limits respiration by promoting the closed configuration of VDAC. Together these results demonstrate that following an apoptotic signal, Bcl-xL can maintain metabolite exchange across the outer Mitochondrial Membrane by inhibiting VDAC closure.
-
the role of the bcl 2 family in the regulation of outer Mitochondrial Membrane permeability
Cell Death & Differentiation, 2000Co-Authors: Marian H Harris, Craig B ThompsonAbstract:Mitochondria are well known as sites of electron transport and generators of cellular ATP. Mitochondria also appear to be sites of cell survival regulation. In the process of programmed cell death, mediators of apoptosis can be released from mitochondria through disruptions in the outer Mitochondrial Membrane; these mediators then participate in the activation of caspases and of DNA degradation. Thus the regulation of outer Mitochondrial Membrane integrity is an important control point for apoptosis. The Bcl-2 family is made up of outer Mitochondrial Membrane proteins that can regulate cell survival, but the mechanisms by which Bcl-2 family proteins act remain controversial. Most metabolites are permeant to the outer Membrane through the voltage dependent anion channel (VDAC), and Bcl-2 family proteins appear to be able to regulate VDAC function. In addition, many Bcl-2 family proteins can form channels in vitro, and some pro-apoptotic members may form multimeric channels large enough to release apoptosis promoting proteins from the interMembrane space. Alternatively, Bcl-2 family proteins have been hypothesized to coordinate the permeability of both the outer and inner Mitochondrial Membranes through the permeability transition (PT) pore. Increasing evidence suggests that alterations in cellular metabolism can lead to pro-apoptotic changes, including changes in intracellular pH, redox potential and ion transport. By regulating Mitochondrial Membrane physiology, Bcl-2 proteins also affect Mitochondrial energy generation, and thus influence cellular bioenergetics. Cell Death and Differentiation (2000) 7, 1182–1191
-
outer Mitochondrial Membrane permeability can regulate coupled respiration and cell survival
Proceedings of the National Academy of Sciences of the United States of America, 2000Co-Authors: Matthew Vander G Heiden, Marco Colombini, Navdeep S Chandel, Xiao Xian Li, Paul T Schumacker, Craig B ThompsonAbstract:Coupled cellular respiration requires that ATP and ADP be efficiently exchanged between the cytosol and the Mitochondrial matrix. When growth factors are withdrawn from dependent cells, metabolism is disrupted by a defect in ATP/ADP exchange across the Mitochondrial Membranes. Unexpectedly, we find that this defect results from loss of outer Mitochondrial Membrane permeability to metabolic anions. This decrease in anion permeability correlates with the changes in conductance properties that accompany closure of the voltage-dependent anion channel (also known as Mitochondrial porin). Loss of outer Membrane permeability (i) results in the accumulation of stored metabolic energy within the interMembrane space in the form of creatine phosphate, (ii) is prevented by the outer Mitochondrial Membrane proteins Bcl-xL and Bcl-2, and (iii) can be reversed by growth factor readdition. If outer Membrane impermeability persists, the disruption of Mitochondrial homeostasis culminates in loss of outer Mitochondrial Membrane integrity, cytochrome c redistribution, and apoptosis. The recognition that outer Membrane permeability is regulated under physiological conditions has important implications for the understanding of bioenergetics and cell survival.
Matthew Freeman - One of the best experts on this subject based on the ideXlab platform.
-
Mitochondrial Membrane remodelling regulated by a conserved rhomboid protease
Nature, 2003Co-Authors: Angus G Mcquibban, Saroj Saurya, Matthew FreemanAbstract:Rhomboid proteins are intraMembrane serine proteases that activate epidermal growth factor receptor (EGFR) signalling in Drosophila1. Rhomboids are conserved throughout evolution2,3,4,5, and even in eukaryotes their existence in species with no EGFRs implies that they must have additional roles. Here we report that Saccharomyces cerevisiae has two rhomboids, which we have named Rbd1p and Rbd2p. RBD1 deletion results in a respiratory defect; consistent with this, Rbd1p is localized in the inner Mitochondrial Membrane and mutant cells have disrupted mitochondria. We have identified two substrates of Rbd1p: cytochrome c peroxidase (Ccp1p); and a dynamin-like GTPase (Mgm1p), which is involved in Mitochondrial Membrane fusion6,7,8,9,10. Rbd1p mutants are indistinguishable from Mgm1p mutants, indicating that Mgm1p is a key substrate of Rbd1p and explaining the rbd1Δ Mitochondrial phenotype. Our data indicate that Mitochondrial Membrane remodelling is regulated by cleavage of Mgm1p and show that intraMembrane proteolysis by rhomboids controls cellular processes other than signalling. In addition, Mitochondrial rhomboids are conserved throughout eukaryotes and the mammalian homologue, PARL11, rescues the yeast mutant, suggesting that these proteins represent a functionally conserved subclass of rhomboid proteases.
-
Mitochondrial Membrane remodelling regulated by a conserved rhomboid protease
Nature, 2003Co-Authors: G. Angus Mcquibban, Saroj Saurya, Matthew FreemanAbstract:Rhomboid proteins are intraMembrane serine proteases that activate epidermal growth factor receptor (EGFR) signalling in Drosophila. Rhomboids are conserved throughout evolution, and even in eukaryotes their existence in species with no EGFRs implies that they must have additional roles. Here we report that Saccharomyces cerevisiae has two rhomboids, which we have named Rbd1p and Rbd2p. RBD1 deletion results in a respiratory defect; consistent with this, Rbd1p is localized in the inner Mitochondrial Membrane and mutant cells have disrupted mitochondria. We have identified two substrates of Rbd1p: cytochrome c peroxidase (Ccp1p); and a dynamin-like GTPase (Mgm1p), which is involved in Mitochondrial Membrane fusion. Rbd1p mutants are indistinguishable from Mgm1p mutants, indicating that Mgm1p is a key substrate of Rbd1p and explaining the rbd1Delta Mitochondrial phenotype. Our data indicate that Mitochondrial Membrane remodelling is regulated by cleavage of Mgm1p and show that intraMembrane proteolysis by rhomboids controls cellular processes other than signalling. In addition, Mitochondrial rhomboids are conserved throughout eukaryotes and the mammalian homologue, PARL, rescues the yeast mutant, suggesting that these proteins represent a functionally conserved subclass of rhomboid proteases.
Patrick R Cammarata - One of the best experts on this subject based on the ideXlab platform.
-
rna suppression of erk2 leads to collapse of Mitochondrial Membrane potential with acute oxidative stress in human lens epithelial cells
American Journal of Physiology-endocrinology and Metabolism, 2008Co-Authors: James M Flynn, Deborah A Lannigan, David E Clark, Margaret H Garner, Patrick R CammarataAbstract:17β-Estradiol (E2) reduces oxidative stress-induced depolarization of Mitochondrial Membrane potential (MMP) in cultured human lens epithelial cells (HLE-B3). The mechanism by which the nongenomic ...
-
17β estradiol stimulates mapk signaling pathway in human lens epithelial cell cultures preventing collapse of Mitochondrial Membrane potential during acute oxidative stress
Mitochondrion, 2005Co-Authors: Andrea N Moor, James M Flynn, Srinivas Gottipati, Frank J Giblin, Patrick R CammarataAbstract:17beta-estradiol (17beta-E2) protects against H2O2-mediated depletion of intracellular ATP and lessens the degree of depolarization of Mitochondrial Membrane potential (DeltaPsi(m)) in cultured lens epithelial cells consequential to oxidative insult. We now report that 17beta-E2 acts as a positive regulator of the survival signal transduction pathway, MAPK which, in turn, acts to stabilize DeltaPsi(m) in effect, attenuating the extent of depolarization of Mitochondrial Membrane potential in the face of acute oxidative stress. The SV-40 viral transformed human cell line, HLE-B3 was treated with 17beta-E2 over a time course of 60 min and phosphorylation of ERK1/2 was analyzed by Western blot. ERK1/2 was phosphorylated within 5-15 min in the presence of 17beta-E2. Cell cultures were exposed to the MEK1/2 inhibitor, UO126, subsequent to H2O2+/-17beta-E2 treatment and the DeltaPsi(m) examined using JC-1, a potentiometric dye which serves as an indicator for the state of Mitochondrial Membrane potential. UO126 treatment attenuated ERK1/2 phosphorylation irrespective of whether estradiol was administered. Mitochondrial Membrane depolarization resulting from H2O2 stress was substantially greater in the presence of UO126. The greater the extent of depolarization, the less effective 17beta-E2 treatment was in checking Mitochondrial Membrane depolarization, indicating that the relative degree of ERK phosphorylation influences Mitochondrial stability with oxidative insult. The data support a positive correlation between 17beta-E2 stimulation of ERK1/2 phosphorylation and Mitochondrial stabilization that would otherwise cause a complete collapse of DeltaPsi(m).
Saroj Chakrabarti - One of the best experts on this subject based on the ideXlab platform.
-
role of oxidative stress Mitochondrial Membrane potential and calcium homeostasis in nickel subsulfide induced human lymphocyte death in vitro
Science of The Total Environment, 2006Co-Authors: Prosper Mbembameka, Nicole Lemieux, Saroj ChakrabartiAbstract:Abstract When isolated human lymphocytes were treated in vitro either with various concentrations (0–2 mM) of soluble form of nickel subsulfide (Ni 3 S 2 ) at 37 °C for 4 h or at various times (0–240 min), both concentration- and time-dependent effects of Ni 3 S 2 on lymphocyte death were observed. Increased generation of hydrogen peroxide (H 2 O 2 ), and superoxide anion (O 2 − ), lipid peroxidation and depletion of both nonprotein (NP-) and protein (P-) sulfhydryl (SH) contents were induced by 1 mM Ni 3 S 2 . Ni 3 S 2 -induced lymphocyte death was significantly prevented by pre-treatment with either catalase (a H 2 O 2 scavenger), or superoxide dismutase (scavenger of O 2 − radical), or dimethylthiourea/mannitol (hydroxyl radical scavengers), or deferoxamine (iron-chelator), or glutathione/ N -acetylcysteine. Co-treatment with cyclosporin A (a Mitochondrial Membrane potential' inhibitor) inhibited Ni 3 S 2 -induced disturbances in Mitochondrial Membrane potential, and significantly prevented Ni 3 S 2 -induced lymphocyte death. Ni 3 S 2 -induced lymphocyte death was also significantly prevented by modulating intracellular calcium fluxes using both Ca 2+ channel blockers and intracellular Ca 2+ antagonists. Thus, the mechanism of soluble Ni 3 S 2 -induced activation of lymphocyte death signalling pathways involves increasing generation of different types of oxidative stress, disturbances in Mitochondrial Membrane potential and cellular calcium homeostasis' destabilization.
-
role of oxidative stress Mitochondrial Membrane potential and calcium homeostasis in nickel sulfate induced human lymphocyte death in vitro
Chemico-Biological Interactions, 2005Co-Authors: Prosper Mbembameka, Nicole Lemieux, Saroj ChakrabartiAbstract:Abstract When isolated human lymphocytes were treated in vitro with various concentrations of nickel sulfate (NiSO4) (0–4 mM) at 37 °C for 4 h, both concentration- and time-dependent effects of NiSO4 on lymphocyte death were observed. Increased generation of hydrogen peroxide, depletion of both nonprotein and protein sulfhydryl contents, and lipid peroxidation were induced by NiSO4. NiSO4-induced lymphocyte death was significantly prevented by pre-treatment with either catalase, or dimethylthiourea/mannitol, or deferoxamine, or excess glutathione/N-acetylcysteine. Cotreatment with cyclosporin A (a specific inhibitor of Mitochondrial Membrane potential) not only inhibited NiSO4-induced Mitochondrial Membrane potential, but also significantly prevented Ni compound-induced lymphocyte death. NiSO4-induced lymphocyte death was also significantly prevented by modulating intracellular calcium fluxes using both Ca2+ channel blockers and intracellular Ca2+ antagonist. Thus, the mechanism of NiSO4-induced activation of lymphocyte death signalling pathways involves not only the excess generation of different types of oxidative stress but also NiSO4-induced loss of Mitochondrial Membrane potential and destabilization of cellular calcium homeostasis as well.
Lan Bo Chen - One of the best experts on this subject based on the ideXlab platform.
-
29 Mitochondrial Membrane potential monitored by jc 1 dye
Methods in Enzymology, 1995Co-Authors: Martin Reers, Cristina Mottolahartshorn, A P Chen, Stephen T Smiley, Lan Bo ChenAbstract:Publisher Summary This chapter focuses on the Mitochondrial Membrane potential monitored by JC-1 dye. It uses JC-1 to investigate the remaining questions about Mitochondrial Membrane potential in living cells, including the component of the electrochemical gradient that is responsible for the formation of J-aggregates, the study of all mitochondria in the same cell does have a similar Membrane potential, and the study of the variation of Membrane potential within a given mitochondrion. The chapter discusses the JC-1 uptake by isolated mitochondria. In these studies using isolated cardiac mitochondria, JC-1 monomers were taken up into the Mitochondrial matrix as a result of changes in the Membrane potential of energized and coupled mitochondria. JC-1 uptake by mitochondria in living cells is presented. For the majority of cell types and cell lines examined, it is possible that all mitochondria in the same cell do not maintain the same Membrane potential.
-
Mitochondrial Membrane potential monitored by jc 1 dye
Methods in Enzymology, 1995Co-Authors: Martin Reers, Cristina Mottolahartshorn, A P Chen, Stephen T Smiley, Mei Lin, Lan Bo ChenAbstract:Publisher Summary This chapter focuses on the Mitochondrial Membrane potential monitored by JC-1 dye. It uses JC-1 to investigate the remaining questions about Mitochondrial Membrane potential in living cells, including the component of the electrochemical gradient that is responsible for the formation of J-aggregates, the study of all mitochondria in the same cell does have a similar Membrane potential, and the study of the variation of Membrane potential within a given mitochondrion. The chapter discusses the JC-1 uptake by isolated mitochondria. In these studies using isolated cardiac mitochondria, JC-1 monomers were taken up into the Mitochondrial matrix as a result of changes in the Membrane potential of energized and coupled mitochondria. JC-1 uptake by mitochondria in living cells is presented. For the majority of cell types and cell lines examined, it is possible that all mitochondria in the same cell do not maintain the same Membrane potential.