Molecular Design of the Voltage-Dependent, Anion-Selective Channel in the Mitochondrial Outer Membrane

1995 ◽  
Vol 114 (1) ◽  
pp. 41-59 ◽  
Author(s):  
Xiao Wei Guo ◽  
P.Ross Smith ◽  
Bernard Cognon ◽  
Dora D'Arcangelis ◽  
Elena Dolginova ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Molecular Design ◽  
Mitochondrial Outer Membrane ◽  
Voltage Dependent ◽  
Selective Channel

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 A C-Terminally Truncated Variant of Neurospora crassa VDAC Assembles Into a Partially Functional Form in the Mitochondrial Outer Membrane and Forms Multimers in vitro

2021 ◽  
Vol 12 ◽  
Author(s):  
Fraser G. Ferens ◽  
William A. T. Summers ◽  
Ameet Bharaj ◽  
Jörg Stetefeld ◽  
Deborah A. Court
Keyword(s):  
Neurospora Crassa ◽  
Outer Membrane ◽  
Analytical Ultracentrifugation ◽  
Size Exclusion ◽  
Mitochondrial Outer Membrane ◽  
Voltage Dependent ◽  
Exclusion Chromatography ◽  
Selective Channel

The voltage-dependent anion-selective channel (VDAC) is a porin in the mitochondrial outer membrane (MOM). Unlike bacterial porins, several mitochondrial β-barrels comprise an odd number of β-strands, as is the case for the 19-β-stranded VDAC. Previously, a variant of a VDAC from Neurospora crassa, VDAC-ΔC, lacking the predicted 19th β-strand, was found to form gated, anion-selective channels in artificial membranes. In vivo, the two C-terminal β-strands (β18 and β19) in VDAC form a β-hairpin necessary for import from the cytoplasm into mitochondria and the β-signal required for assembly in the mitochondrial outer membrane resides in β19. The current study demonstrated that the putative 18-stranded β-barrel formed by VDAC-ΔC can be imported and assembled in the MOM in vivo and can also partially rescue the phenotype associated with the deletion of VDAC from a strain of N. crassa. Furthermore, when expressed and purified from Escherichia coli, VDAC-ΔC can be folded into a β-strand-rich form in decyl-maltoside. Size exclusion chromatography (SEC) alone or combined with multi-angle light scattering (SEC-MALS) and analytical ultracentrifugation revealed that, unlike full-length VDACs, VDAC-ΔC can self-organize into dimers and higher order oligomers in the absence of sterol.

scholarly journals The Biogenesis Process of VDAC – From Early Cytosolic Events to Its Final Membrane Integration

2021 ◽  
Vol 12 ◽  
Author(s):  
Anasuya Moitra ◽  
Doron Rapaport
Keyword(s):  
Outer Membrane ◽  
Nuclear Dna ◽  
Current Knowledge ◽  
Yeast Cells ◽  
Mitochondrial Outer Membrane ◽  
Voltage Dependent ◽  
Selective Channel ◽  
Targeting Signal ◽  
Cytosolic Factors

Voltage dependent anion-selective channel (VDAC) is the most abundant protein in the mitochondrial outer membrane. It is a membrane embedded β-barrel protein composed of 19 mostly anti-parallel β-strands that form a hydrophilic pore. Similar to the vast majority of mitochondrial proteins, VDAC is encoded by nuclear DNA, and synthesized on cytosolic ribosomes. The protein is then targeted to the mitochondria while being maintained in an import competent conformation by specific cytosolic factors. Recent studies, using yeast cells as a model system, have unearthed the long searched for mitochondrial targeting signal for VDAC and the role of cytosolic chaperones and mitochondrial import machineries in its proper biogenesis. In this review, we summarize our current knowledge regarding the early cytosolic stages of the biogenesis of VDAC molecules, the specific targeting of VDAC to the mitochondrial surface, and the subsequent integration of VDAC into the mitochondrial outer membrane by the TOM and TOB/SAM complexes.

scholarly journals Ca2+-dependent Control of the Permeability Properties of the Mitochondrial Outer Membrane and Voltage-dependent Anion-selective Channel (VDAC)

2006 ◽  
Vol 281 (25) ◽  
pp. 17347-17358 ◽  
Author(s):  
György Báthori ◽  
György Csordás ◽  
Cecilia Garcia-Perez ◽  
Erika Davies ◽  
György Hajnóczky
Keyword(s):  
Outer Membrane ◽  
Mitochondrial Outer Membrane ◽  
Voltage Dependent ◽  
Selective Channel

scholarly journals The Voltage-Dependent Anion Selective Channel 1 (VDAC1) Topography in the Mitochondrial Outer Membrane as Detected in Intact Cell

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e81522 ◽  
Author(s):  
Marianna F. Tomasello ◽  
Francesca Guarino ◽  
Simona Reina ◽  
Angela Messina ◽  
Vito De Pinto
Keyword(s):  
Outer Membrane ◽  
Intact Cell ◽  
Mitochondrial Outer Membrane ◽  
Voltage Dependent ◽  
Selective Channel

scholarly journals Direct Membrane Insertion of Voltage-dependent Anion-selective Channel Protein Catalyzed by Mitochondrial Tom20

1999 ◽  
Vol 145 (5) ◽  
pp. 973-978 ◽  
Author(s):  
Enrico Schleiff ◽  
John R. Silvius ◽  
Gordon C. Shore
Keyword(s):  
Outer Membrane ◽  
Mitochondrial Outer Membrane ◽  
Temperature Sensitive ◽  
Fully Integrated ◽  
Channel Protein ◽  
Transmembrane Channel ◽  
Voltage Dependent ◽  
Selective Channel ◽  
Import Receptors ◽  
Preprotein Translocation

Insertion of newly synthesized proteins into or across the mitochondrial outer membrane is initiated by import receptors at the surface of the organelle. Typically, this interaction directs the precursor protein into a preprotein translocation pore, comprised of Tom40. Here, we show that a prominent β-barrel channel protein spanning the outer membrane, human voltage- dependent anion-selective channel (VDAC), bypasses the requirement for the Tom40 translocation pore during biogenesis. Insertion of VDAC into the outer membrane is unaffected by plugging the translocation pore with a partially translocated matrix preprotein, and mitochondria containing a temperature-sensitive mutant of Tom40 insert VDAC at the nonpermissive temperature. Synthetic liposomes harboring the cytosolic domain of the human import receptor Tom20 efficiently insert newly synthesized VDAC, resulting in transbilayer transport of ATP.  Therefore, Tom20 transforms newly synthesized cytosolic VDAC into a transmembrane channel that is fully integrated into the lipid bilayer.

Cryo-Electron Microscopy and Correlation Averaging of Frozen-Hydrated, Polymorphic 2D Crystals of the Mitochondrial Outer Membrane Channel

1990 ◽  
Vol 48 (1) ◽  
pp. 100-101
Author(s):  
Xiao-Wei Guo
Keyword(s):  
Outer Membrane ◽  
Hexagonal Lattice ◽  
Mitochondrial Outer Membrane ◽  
Rectangular Lattice ◽  
Electron Microscopic ◽  
Cryo Electron Microscopy ◽  
Voltage Dependent ◽  
Outer Membrane Channel ◽  
2D Crystals ◽  
Vdac Channel

Voltage-dependent, anion-selective channels (VDAC) are formed in the mitochondrial outer membrane (mitOM) by a 30-kDa polypeptide. These channels form ordered 2D arrays when mitOMs from Neurospora crassa are treated with soluble phospholipase A2. We obtain low-dose electron microscopic images of unstained specimens of VDAC crystals preserved in vitreous ice, using a Philips EM420 equipped with a Gatan cryo-transfer stage. We then use correlation analysis to compute average projections of the channel crystals. The procedure involves Fourier-filtration of a region within a crystal field to obtain a preliminary average that is subsequently cross-correlated with the entire crystal. Subregions are windowed from the crystal image at coordinates of peaks in the cross-correlation function (CCF, see Figures 1 and 2) and summed to form averages (Figure 3).The VDAC channel forms several different types of crystalline arrays in mitOMs. The polymorph first observed during phospholipase treatment is a parallelogram array (a=13 run, b=11.5 run, θ==109°) containing 6 water-filled pores per unit cell. Figure 1 shows the CCF of a sub-field of such an “oblique” array used to compute the correlation average of Figure 3A. With increased phospholipase treatment, other polymorphs are observed, often co-existing within the same crystal. For example, two distinct (but closely related) types of lattices occur in the field corresponding to the CCF of Figure 2: a “contracted” version of the parallelogram lattice (a=13 run, b=10 run, θ=99°), and a near-rectangular lattice (a=8.5 run, b=5 nm). The pattern of maxima in this CCF suggests that a third, near-hexagonal lattice (a=4.5 nm) may also be present. The correlation averages of Figures 3B-D were computed from polycrystalline fields, using peak coordinates in regions of CCFs corresponding to each of the three lattice types.

Effects of cytochrome c on the mitochondrial apoptosis-induced channel MAC

2004 ◽  
Vol 286 (5) ◽  
pp. C1109-C1117 ◽  
Author(s):  
Liang Guo ◽  
Dawn Pietkiewicz ◽  
Evgeny V. Pavlov ◽  
Sergey M. Grigoriev ◽  
John J. Kasianowicz ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Outer Membrane ◽  
Cell Types ◽  
Rnase A ◽  
Mitochondrial Outer Membrane ◽  
Dependent Manner ◽  
Mitochondrial Apoptosis ◽  
Noise Type ◽  
Voltage Dependent

Recent studies indicate that cytochrome c is released early in apoptosis without loss of integrity of the mitochondrial outer membrane in some cell types. The high-conductance mitochondrial apoptosis-induced channel (MAC) forms in the outer membrane early in apoptosis of FL5.12 cells. Physiological (micromolar) levels of cytochrome c alter MAC activity, and these effects are referred to as types 1 and 2. Type 1 effects are consistent with a partitioning of cytochrome c into the pore of MAC and include a modest decrease in conductance that is dose and voltage dependent, reversible, and has an increase in noise. Type 2 effects may correspond to “plugging” of the pore or destabilization of the open state. Type 2 effects are a dose-dependent, voltage-independent, and irreversible decrease in conductance. MAC is a heterogeneous channel with variable conductance. Cytochrome c affects MAC in a pore size-dependent manner, with maximal effects of cytochrome c on MAC with conductance of 1.9–5.4 nS. The effects of cytochrome c, RNase A, and high salt on MAC indicate that size, rather than charge, is crucial. The effects of dextran molecules of various sizes indicate that the pore diameter of MAC is slightly larger than that of 17-kDa dextran, which should be sufficient to allow the passage of 12-kDa cytochrome c. These findings are consistent with the notion that MAC is the pore through which cytochrome c is released from mitochondria during apoptosis.

scholarly journals Identification of two voltage-dependent anion channel-like protein sequences conserved in Kinetoplastida

2012 ◽  
Vol 8 (3) ◽  
pp. 446-449 ◽  
Author(s):  
Nadine Flinner ◽  
Enrico Schleiff ◽  
Oliver Mirus
Keyword(s):  
Outer Membrane ◽  
Trypanosoma Brucei ◽  
Protein Sequences ◽  
Anion Channel ◽  
Mitochondrial Outer Membrane ◽  
Voltage Dependent Anion Channel ◽  
Voltage Dependent

The eukaryotic porin superfamily consists of two families, voltage-dependent anion channel (VDAC) and Tom40, which are both located in the mitochondrial outer membrane. In Trypanosoma brucei , only a single member of the VDAC family has been described. We report the detection of two additional eukaryotic porin-like sequences in T. brucei . By bioinformatic means, we classify both as putative VDAC isoforms.

Sign in / Sign up

Export Citation Format

Share Document