Lipids in Regulation of the Mitochondrial Outer Membrane Permeability, Bioenergetics, and Metabolism

2017 ◽  
pp. 185-215 ◽  
Author(s):  
Tatiana K. Rostovtseva ◽  
David P. Hoogerheide ◽  
Amandine Rovini ◽  
Sergey M. Bezrukov
Keyword(s):  
Membrane Permeability ◽  
Outer Membrane ◽  
Mitochondrial Outer Membrane ◽  
Outer Membrane Permeability

scholarly journals Regulation of Respiration in Permeabilized Muscle Cells: Apparent KM for ADP Shows the Mitochondrial Outer Membrane Permeability

2013 ◽  
Vol 104 (2) ◽  
pp. 447a-448a
Author(s):  
Rafaela Bagur Quetglas ◽  
Minna Karu-Varikmaa ◽  
Kersti Tepp ◽  
Madis Metsis ◽  
Tuuli Kaambre ◽  
...  
Keyword(s):  
Membrane Permeability ◽  
Outer Membrane ◽  
Muscle Cells ◽  
Mitochondrial Outer Membrane ◽  
Regulation Of Respiration ◽  
Outer Membrane Permeability ◽  
Permeabilized Muscle

Phosphorothioate oligonucleotides reduce mitochondrial outer membrane permeability to ADP

2007 ◽  
Vol 292 (4) ◽  
pp. C1388-C1397 ◽  
Author(s):  
Wenzhi Tan ◽  
Johnathan C. Lai ◽  
Paul Miller ◽  
C. A. Stein ◽  
Marco Colombini
Keyword(s):  
Cytochrome C ◽  
Membrane Permeability ◽  
Outer Membrane ◽  
Mitochondrial Outer Membrane ◽  
Cytochrome C Release ◽  
Voltage Dependent ◽  
Selective Channel ◽  
Vdac Channels ◽  
Outer Membrane Permeability ◽  
Apoptotic Cascade

G3139, an antisense Bcl-2 phosphorothioate oligodeoxyribonucleotide, induces apoptosis in melanoma and other cancer cells. This apoptosis happens before and in the absence of the downregulation of Bcl-2 and thus seems to be Bcl-2-independent. Binding of G3139 to mitochondria and its ability to close voltage-dependent anion-selective channel (VDAC) have led to the hypothesis that G3139 acts, in part, by interacting with VDAC channels in the mitochondrial outer membrane ( 21 ). In this study, we demonstrate that G3139 is able to reduce the mitochondrial outer membrane permeability to ADP by a factor of 6 or 7 with a Ki between 0.2 and 0.5 μM. Because VDAC is responsible for this permeability, this result strengthens the aforesaid hypothesis. Other mitochondrial respiration components are not affected by [G3139] up to 1 μM. Higher levels begin to inhibit respiration rates, decrease light scattering and increase uncoupled respiration. These results agree with accumulating evidence that VDAC closure favors cytochrome c release. The speed of this effect (within 10 min) places it early in the apoptotic cascade with cytochrome c release occurring at later times. Other phosphorothioate oligonucleotides are also able to induce VDAC closure, and there is some length dependence. The phosphorothioate linkages are required to induce the reduction of outer membrane permeability. At levels below 1 μM, phosphorothioate oligonucleotides are the first specific tools to restrict mitochondrial outer membrane permeability.

scholarly journals Activation of Piezo1 sensitizes cells to TRAIL-mediated apoptosis through mitochondrial outer membrane permeability

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Jacob M. Hope ◽  
Maria Lopez-Cavestany ◽  
Wenjun Wang ◽  
Cynthia A. Reinhart-King ◽  
Michael R. King
Keyword(s):  
Shear Stress ◽  
Computational Model ◽  
Cancer Cells ◽  
Membrane Permeability ◽  
Outer Membrane ◽  
Calcium Influx ◽  
Mitochondrial Outer Membrane ◽  
Reduce Shear Stress ◽  
Static Conditions ◽  
Outer Membrane Permeability

Abstract TRAIL specifically induces apoptosis in cancer cells without affecting healthy cells. However, TRAIL’s cancer cytotoxicity was insufficient in clinical trials. Circulatory-shear stress is known to sensitize cancer cells to TRAIL. In this study, we examine the mechanism of this TRAIL sensitization with the goal of translating it to static conditions. GsMTx-4, a Piezo1 inhibitor, was found to reduce shear stress-related TRAIL sensitization, implicating Piezo1 activation as a potential TRAIL-sensitizer. The Piezo1 agonist Yoda1 recreated shear stress-induced TRAIL sensitization under static conditions. A significant increase in apoptosis occurred when PC3, COLO 205, or MDA-MB-231 cells were treated with Yoda1 and TRAIL in combination, but not in Bax-deficient DU145 cells. Calpastatin inhibited apoptosis in Yoda1-TRAIL treated cells, indicating that calpain activation is necessary for apoptosis by Yoda1 and TRAIL. Yoda1 and TRAIL treated PC3 cells showed increased mitochondrial outer membrane permeability (MOMP), mitochondrial depolarization, and activated Bax. This implies that Piezo1 activation sensitizes cancer cells to TRAIL through a calcium influx that activates calpains. The Calpains then induce MOMP by enhancing Bax activation. From these experiments a computational model was developed to simulate apoptosis for cells treated with TRAIL and increased calcium. The computational model elucidated the proapoptotic or antiapoptotic roles of Bax, Bcl-2, XIAP, and other proteins important in the mitochondrial-apoptotic signaling pathway.

scholarly journals Mitochondrial Outer Membrane Permeability Change and Hypersensitivity to Digitonin Early in Staurosporine-induced Apoptosis

2002 ◽  
Vol 278 (2) ◽  
pp. 1346-1353 ◽  
Author(s):  
Shili Duan ◽  
Petr Hájek ◽  
Catherine Lin ◽  
Soo Kyung Shin ◽  
Giuseppe Attardi ◽  
...  
Keyword(s):  
Membrane Permeability ◽  
Outer Membrane ◽  
Mitochondrial Outer Membrane ◽  
Permeability Change ◽  
Induced Apoptosis ◽  
Outer Membrane Permeability
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