scholarly journals c-Myc induces cytochrome c release in Rat1 fibroblasts by increasing outer mitochondrial membrane permeability in a Bid-dependent manner

2003 ◽  
Vol 10 (5) ◽  
pp. 599-608 ◽  
Author(s):  
I Iaccarino ◽  
D Hancock ◽  
G Evan ◽  
J Downward
Keyword(s):  
Cytochrome C ◽  
Membrane Permeability ◽  
Mitochondrial Membrane ◽  
Dependent Manner ◽  
Outer Mitochondrial Membrane ◽  
Cytochrome C Release ◽  
Mitochondrial Membrane Permeability

scholarly journals Downregulation of KDR expression induces apoptosis in breast cancer cells

2014 ◽  
Vol 19 (4) ◽  
Author(s):  
Xiao Zhang ◽  
Yin-Lin Ge ◽  
Shu-Ping Zhang ◽  
Ping Yan ◽  
Run-Hua Tian
Keyword(s):  
Breast Cancer ◽  
Cytochrome C ◽  
Membrane Permeability ◽  
Human Breast Cancer ◽  
Mitochondrial Membrane ◽  
Caspase 3 ◽  
Human Breast ◽  
Cytochrome C Release ◽  
Mitochondrial Membrane Permeability ◽  
Mcf 7

AbstractAngiogenesis plays a crucial role in the growth, invasion and metastasis of breast cancer. Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are the key regulators of tumor angiogenesis. VEGFR-2, known as the kinase insert domain receptor (KDR), is a key receptor involved in malignant angiogenesis. We previously showed that knocking down KDR with short interference RNA (KDR-siRNA) markedly decreased KDR expression and suppressed tumor growth in a xenograft model. However, the mechanisms underlying the anti-cancer effects of KDR-siRNA are not clearly understood. This study aimed to elucidate the molecular mechanisms that induce apoptosis in human breast cancer MCF-7 cells after transfection with KDR-siRNA. We studied the effects of KDR-siRNA on proliferation, apoptosis, antiapoptotic and pro-apoptotic proteins, mitochondrial membrane permeability, cytochrome c release and caspase-3 activity. The results indicated that KDR-siRNA treatment significantly inhibited the proliferation and induced the apoptosis of MCF-7 cells, reduced the levels of the anti-apoptotic proteins, Bcl-2 and Bcl-xl, and increased the level of the pro-apoptotic protein Bax, resulting in a decreased Bcl-2/Bax ratio. KDR-siRNA also enhanced the mitochondrial membrane permeability, induced cytochrome c release from the mitochondria, upregulated apoptotic protease-activating factor-1 (Apaf-1), cleaved caspase-3, and increased caspase-3 activity in MCF-7 cells. Furthermore, KDR-siRNA-induced apoptosis in MCF-7 cells was blocked by the caspase inhibitor Z-VAD-FMK, suggesting a role of caspase activation in the induction of apoptosis. These results indicate that the Bcl-2 family proteins and caspase-related mitochondrial pathways are primarily involved in KDR-siRNAinduced apoptosis in MCF-7 cells and that KDR might be a potential therapeutic target for human breast cancer treatments.

scholarly journals Outer mitochondrial membrane permeability can regulate coupled respiration and cell survival

2000 ◽  
Vol 97 (9) ◽  
pp. 4666-4671 ◽  
Author(s):  
M. G. Vander Heiden ◽  
N. S. Chandel ◽  
X. X. Li ◽  
P. T. Schumacker ◽  
M. Colombini ◽  
...  
Keyword(s):  
Cell Survival ◽  
Membrane Permeability ◽  
Mitochondrial Membrane ◽  
Outer Mitochondrial Membrane ◽  
Mitochondrial Membrane Permeability

scholarly journals Which Domain of VDAC2 is Necessary for Bak Insertion to the Outer Mitochondrial Membrane and tBid - Induced Cytochrome C Release?

2013 ◽  
Vol 104 (2) ◽  
pp. 656a ◽  
Author(s):  
Shamim Naghdi ◽  
Peter Varnai ◽  
Soumya Sinha Roy ◽  
Laszlo Hunyady ◽  
Gyorgy Hajnoczky
Keyword(s):  
Cytochrome C ◽  
Mitochondrial Membrane ◽  
Outer Mitochondrial Membrane ◽  
Cytochrome C Release

scholarly journals Mitochondria-Associated Membranes (MAMs) are involved in Bax mitochondrial localization and cytochrome c release

2018 ◽  
Author(s):  
Alexandre Légiot ◽  
Claire Céré ◽  
Thibaud Dupoiron ◽  
Mohamed Kaabouni ◽  
Stéphen Manon
Keyword(s):  
Endoplasmic Reticulum ◽  
Cytochrome C ◽  
Mitochondrial Membrane ◽  
Human Protein ◽  
Outer Mitochondrial Membrane ◽  
Yeast Mutant ◽  
Mitochondrial Localization ◽  
Cytochrome C Release ◽  
Apoptotic Protein

AbstractThe distribution of the pro-apoptotic protein Bax in the outer mitochondrial membrane (OMM) is a central point of regulation of apoptosis. It is now widely recognized that parts of the endoplasmic reticulum (ER) are closely associated to the OMM, and are actively involved in different signalling processes. We adressed a possible role of these domains, called Mitochondria-Associated Membranes (MAMs) in Bax localization and fonction, by expressing the human protein in a yeast mutant deleted of MDM34, a ERMES component (ER-Mitochondria Encounter Structure). By affecting MAMs stability, the deletion of MDM34 altered Bax mitochondrial localization, and decreased its capacity to release cytochrome c. Furthermore, the deletion of MDM34 decreased the size of an uncompletely released, MAMs-associated pool of cytochrome c.

Geraniin induces apoptotic cell death in human lung adenocarcinoma A549 cells in vitro and in vivo

2013 ◽  
Vol 91 (12) ◽  
pp. 1016-1024 ◽  
Author(s):  
Jia Li ◽  
Siran Wang ◽  
Jimei Yin ◽  
Linna Pan
Keyword(s):  
Cytochrome C ◽  
Mitochondrial Membrane ◽  
Apoptotic Cell ◽  
A549 Cells ◽  
Tumor Growth Inhibition ◽  
Dependent Manner ◽  
Cytochrome C Release ◽  
Lung Adenocarcinoma A549

Geraniin has previously been reported to possess extensive biological activity. In this study, we reported that geraniin is an inhibitor of tumor activity in vitro and in vivo. Geraniin suppressed the proliferation of A549 cells in a dose- and time-dependent manner. Geraniin arrested the cell cycle in the S phase and induced a significant accumulation of reactive oxygen species (ROS), as well as an increased percentage of cells with mitochondrial membrane potential (MMP) disruption. Western blot analysis showed that geraniin inhibited Bcl-2 expression and induced Bax expression to disintegrate the outer mitochondrial membrane and cause cytochrome c release. Mitochondrial cytochrome c release was associated with the activation of caspase-9 and caspase-3 cascades. Additionally, geraniin resulted in tumor growth inhibition in A549 xenografts. Our results indicate cytotoxic activity of geraniin towards cancer cells in vitro and in vivo.

scholarly journals The Mitochondrial TOM Complex Is Required for tBid/Bax-induced Cytochrome c Release

2007 ◽  
Vol 282 (38) ◽  
pp. 27633-27639 ◽  
Author(s):  
Martin Ott ◽  
Erik Norberg ◽  
Katharina M. Walter ◽  
Patrick Schreiner ◽  
Christian Kemper ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cytochrome C ◽  
Outer Membrane ◽  
Recombinant Proteins ◽  
Mitochondrial Membrane ◽  
Mitochondrial Outer Membrane ◽  
Intermembrane Space ◽  
Outer Mitochondrial Membrane ◽  
Cytochrome C Release ◽  
Unknown Mechanism

Cytochrome c release from mitochondria is a key event in apoptosis signaling that is regulated by Bcl-2 family proteins. Cleavage of the BH3-only protein Bid by multiple proteases leads to the formation of truncated Bid (tBid), which, in turn, promotes the oligomerization/insertion of Bax into the mitochondrial outer membrane and the resultant release of proteins residing in the intermembrane space. Bax, a monomeric protein in the cytosol, is targeted by a yet unknown mechanism to the mitochondria. Several hypotheses have been put forward to explain this targeting specificity. Using mitochondria isolated from different mutants of the yeast Saccharomyces cerevisiae and recombinant proteins, we have now investigated components of the mitochondrial outer membrane that might be required for tBid/Bax-induced cytochrome c release. Here, we show that the protein translocase of the outer mitochondrial membrane is required for Bax insertion and cytochrome c release.

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