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1.
A soluble protein isolated from mitochondria has been found to modulate the voltage-dependent properties of the mitochondrial outer membrane channel, VDAC. This protein, called the VDAC modulator, was first found inNeurospora crassa and then discovered in species from other eukaryotic kingdoms. The modulator-containing fraction (at a crude protein concentration of 20 µg/ml) increases the voltage dependence of VDAC channels over 2–3-fold. At higher protein concentrations (50–100 µg/ml), some channels seem to remain in a closed state or be blocked while others display the higher voltage dependence and are able to close at low membrane potentials. By increasing the steepness of the voltage-dependent properties of VDAC channels, this modulator may serve as an amplifierin vivo to increase the sensitivity of the channels in response to changes in the cell's microenvironment, and consequently, regulate the metabolic flux across the outer mitochondrial membrane by controlling the gating of VDAC channels. 相似文献
2.
Nina Antos Olgierd Stobienia Małgorzata Budzińska Hanna Kmita 《Journal of bioenergetics and biomembranes》2001,33(2):119-126
Thus far, only three channel-forming activities have been identified in the outer membrane of the yeast Saccharomyces cerevisiae mitochondria. Two of them, namely the TOM complex channel (translocase of the outer membrane) and the PSC (peptide-sensitive channel) participate in protein translocation and are probably identical, whereas a channel-forming protein called VDAC (voltage-dependent anion channel) serves as the major pathway for metabolites. The VDAC is present in two isoforms (VDAC1 and VDAC2) of which only VDAC1 has been shown to display channel-forming activity. Moreover, the permeability of VDAC1 has been reported to be limited in uncoupled mitochondria of S. cerevisiae. The presented data indicate that in S. cerevisiae-uncoupled mitochondria, external NADH, applied at higher concentrations (above 50 nmoles per 0.1 mg of mitochondrial protein), may use the TOM complex channel, besides VDAC1, to cross the outer membrane. Thus, the permeability of VDAC1 could be a limiting step in transport of external NADH across the outer membrane and might be supplemented by the TOM complex channel. 相似文献
3.
Michael Forte Dawn Adelsberger-Mangan Marco Colombini 《The Journal of membrane biology》1987,99(1):65-72
Summary The outer mitochondrial membranes of all organisms so far examined contain a protein which forms voltage-dependent anion selective channels (VDAC) when incorporated into planar phospholipid membranes. Previous reports have suggested that the yeast (Saccharomyces cerevisiae) outer mitochondrial membrane component responsible for channel formation is a protein of 29,000 daltons which is also the major component of this membrane. In this report, we describe the purification of this 29,000-dalton protein to virtual homogeneity from yeast outer mitochondrial membranes. The purified protein readily incorporates into planar phospholipid membranes to produce ionic channels. Electrophysiological characterization of these channels has demonstrated they have a size, selectivity and voltage dependence similar to VDAC from other organisms. Biochemically, the purified protein has been characterized by determining its amino acid composition and isoelectric point (pI). In addition, we have shown that the purified protein, when reconstituted into liposomes, can bind hexokinase in a glucose-6-phosphate dependent manner, as has been shown for VDAC purified from other sources. Since physiological characterization suggests that the functional parameters of this protein have been conserved, antibodies specific to yeast VDAC have been used to assess antigenic conservation among mitochondrial proteins from a wide number of species. These experiments have shown that yeast VDAC antibodies will recognize single mitochondrial proteins fromDrosophila, Dictyostelium andNeurospora of the appropriate molecular weight to be VDAC from these organisms. No reaction was seen to any mitochondrial protein from rat liver, rainbow trout,Paramecium, or mung bean. In addition, yeast VDAC antibodies will recognize a 50-kDa mol wt protein present in tobacco chloroplasts. These results suggest that there is some antigenic as well as functional conservation among different VDACs. 相似文献
4.
Autodirected insertion: preinserted VDAC channels greatly shorten the delay to the insertion of new channels.
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VDAC, a mitochondrial outer membrane channel, has the ability to catalyze and direct the insertion of other VDAC channels into planar phospholipid membranes. The spontaneous rate of insertion of detergent-solubilized VDAC channels into phospholipid membranes is estimated to be 1.5 x 10(-5) channels min-1 micron-2. VDAC channels already in the membrane can increase this rate by a factor of 10(9). The presence of 5 M urea on the opposite side of the membrane increases this 10-fold to 4.5 x 10(5) channels min-1 microns-2. Similar but weaker effects are observed with Triton X100 addition (10(-3)% (v/v)). These agents are not acting on uninserted channels because they do not affect the delay from sample addition to first insertion. Under the chosen conditions, this delay is long (240 s) without preinserted channels. However, the presence of a few VDAC channels in the membrane reduces this delay to 14 s, close to the diffusion limit. Therefore, urea and Triton, added to the side of the membrane opposite that to which the VDAC sample was added, likely increase the flexibility of the VDAC channels in the membrane, allowing them to be more efficient catalysts for VDAC insertion. There are obvious implications for membrane protein insertion and targeting. 相似文献
5.
Multicopy suppressors of phenotypes resulting from the absence of yeast VDAC encode a VDAC-like protein. 总被引:2,自引:2,他引:2
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E Blachly-Dyson J Song W J Wolfgang M Colombini M Forte 《Molecular and cellular biology》1997,17(10):5727-5738
The permeability of the outer mitochondrial membrane to most metabolites is believed to be based in an outer membrane, channel-forming protein known as VDAC (voltage-dependent anion channel). Although multiple isoforms of VDAC have been identified in multicellular organisms, the yeast Saccharomyces cerevisiae has been thought to contain a single VDAC gene, designated POR1. However, cells missing the POR1 gene (delta por1) were able to grow on yeast media containing a nonfermentable carbon source (glycerol) but not on such media at elevated temperature (37 degrees C). If VDAC normally provides the pathway for metabolites to pass through the outer membrane, some other protein(s) must be able to partially substitute for that function. To identify proteins that could functionally substitute for POR1, we have screened a yeast genomic library for genes which, when overexpressed, can correct the growth defect of delta por1 yeast grown on glycerol at 37 degrees C. This screen identified a second yeast VDAC gene, POR2, encoding a protein (YVDAC2) with 49% amino acid sequence identity to the previously identified yeast VDAC protein (YVDAC1). YVDAC2 can functionally complement defects present in delta por1 strains only when it is overexpressed. Deletion of the POR2 gene alone had no detectable phenotype, while yeasts with deletions of both the POR1 and POR2 genes were viable and able to grow on glycerol at 30 degrees C, albeit more slowly than delta por1 single mutants. Like delta por1 single mutants, they could not grow on glycerol at 37 degrees C. Subcellular fractionation studies with antibodies which distinguish YVDAC1 and YVDAC2 indicate that YVDAC2 is normally present in the outer mitochondrial membrane. However, no YVDAC2 channels were detected electrophysiologically in reconstituted systems. Therefore, mitochondrial membranes made from wild-type cells, delta por1 cells, delta por1 delta por2 cells, and delta por1 cells overexpressing YVDAC2 were incorporated into liposomes and the permeability of resulting liposomes to nonelectrolytes of different sizes was determined. The results indicate that YVDAC2 does not confer any additional permeability to these liposomes, suggesting that it may not normally form a channel. In contrast, when the VDAC gene from Drosophila melanogaster was expressed in delta por1 yeast cells, VDAC-like channels could be detected in the mitochondria by both bilayer and liposome techniques, yet the cells failed to grow on glycerol at 37 degrees C. Thus, channel-forming activity does not seem to be either necessary or sufficient to restore growth on nonfermentable carbon sources, indicating that VDAC mediates cellular functions that do not depend on the ability to form channels. 相似文献
6.
Mouse VDAC Isoforms Expressed in Yeast: Channel Properties and Their Roles in Mitochondrial Outer Membrane Permeability 总被引:6,自引:0,他引:6
X. Xu W. Decker M.J. Sampson W.J. Craigen M. Colombini 《The Journal of membrane biology》1999,170(2):89-102
The channel-forming protein called VDAC forms the major pathway in the mitochondrial outer membrane and controls metabolite
flux across that membrane. The different VDAC isoforms of a species may play different roles in the regulation of mitochondrial
functions. The mouse has three VDAC isoforms (VDAC1, VDAC2 and VDAC3). These proteins and different versions of VDAC3 were
expressed in yeast cells (S. cerevisiae) missing the major yeast VDAC gene and studied using different approaches. When reconstituted into liposomes, each isoform
induced a permeability in the liposomes with a similar molecular weight cutoff (between 3,400 and 6,800 daltons based on permeability
to polyethylene glycol). In contrast, electrophysiological studies on purified proteins showed very different channel properties.
VDAC1 is the prototypic version whose properties are highly conserved among other species. VDAC2 also has normal gating activity
but may exist in 2 forms, one with a lower conductance and selectivity. VDAC3 can also form channels in planar phospholipid
membranes. It does not insert readily into membranes and generally does not gate well even at high membrane potentials (up
to 80 mV). Isolated mitochondria exhibit large differences in their outer membrane permeability to NADH depending on which
of the mouse VDAC proteins was expressed. These differences in permeability could not simply be attributed to different amounts
of each protein present in the isolated mitochondria. The roles of these different VDAC proteins are discussed.
Received: 19 June 1998/Revised: 1 April 1999 相似文献
7.
Rostovtseva TK Antonsson B Suzuki M Youle RJ Colombini M Bezrukov SM 《The Journal of biological chemistry》2004,279(14):13575-13583
During apoptosis, cytochrome c is released from mitochondria into the cytosol, where it participates in caspase activation. Various and often conflicting mechanisms have been proposed to account for the increased permeability of the mitochondrial outer membrane that is responsible for this process. The voltage-dependent anion channel (VDAC) is the major permeability pathway for metabolites in the mitochondrial outer membrane and therefore is a very attractive candidate for cytochrome c translocation. Here, we report that properties of VDAC channels reconstituted into planar phospholipid membranes are unaffected by addition of the pro-apoptotic protein Bax under a variety of conditions. Contrary to other reports (Shimizu, S., Narita, M., and Tsujimoto, Y. (1999) Nature 399, 483-487; Shimizu, S., Ide, T., Yanagida, T., and Tsujimoto, Y. (2000) J. Biol. Chem. 275, 12321-12325; Shimizu, S., Konishi, A., Kodama, T., and Tsujimoto, Y. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 3100-3105), we found no electrophysiologically detectable interaction between VDAC channels isolated from mammalian mitochondria and either monomeric or oligomeric forms of Bax. We conclude that Bax does not induce cytochrome c release by acting on VDAC. In contrast to Bax, another pro-apoptotic protein (Bid) proteolytically cleaved with caspase-8 affected the voltage gating of VDAC by inducing channel closure. We speculate that by decreasing the probability of VDAC opening, Bid reduces metabolite exchange between mitochondria and the cytosol, leading to mitochondrial dysfunction. 相似文献
8.
Bcl-2 family of proteins: life-or-death switch in mitochondria 总被引:9,自引:0,他引:9
Tsujimoto Y 《Bioscience reports》2002,22(1):47-58
An increase in the permeability of outer mitochondrial membrane is central to apoptotic cell death, and results in the release of several apoptogenic factors such as cytochrome c into the cytoplasm to activate downstream destructive programs. The voltage-dependent anion channel (VDAC or mitochondrial porin) plays an essential role in disrupting the mitochondrial membrane barrier and is regulated directly by members of the Bcl-2 family proteins. Anti-apoptotic Bcl-2 family members interact with and close the VDAC, whereas some, but not all, proapoptotic members interact with VDAC to open protein-conducting pore through which apoptogenic factors pass. Although the VDAC is involved directly in breaking the mitochondrial membrane barrier and is a known component of the permeability transition pore complex, VDAC-dependent increase in outer membrane permeability can be independent of the permeability transition event such as mitochondrial swelling followed by rupture of the outer mitochondrial membrane. VDAC interacts not only with Bcl-2 family members but also with proteins such as gelsolin, an actin regulatory protein, and appears to be a convergence point for a variety of cell survival and cell death signals. 相似文献
9.
The mitochondrial outer membrane channel, VDAC, is thought to serve as the major permeability pathway for metabolite flux
between the cytoplasm and mitochondria. The permeability of VDAC to citrate, succinate, and phosphate was studied in channels
reconstituted into planar phospholipid membranes. All ions showed large changes in permeability depending on whether the channel
was in the open or in the low conductance, ``closed' state, with the closed state always more cation selective. This was
especially true for the divalent and trivalent anions. Additionally, the anion flux when the voltage was zero was shown to
decrease to 5–11% of the open state flux depending on the anion studied. These results give the first rigorous examination
of the ability of metabolites to permeate through VDAC channels and indicate that these channels can control the flux of these
ions through the outer membrane. This lends more evidence to the growing body of experiments that suggest that the outer mitochondrial
membrane has a much more important role in controlling mitochondrial activity than has been thought historically.
Received: 4 November 1996/Revised: 8 January 1997 相似文献
10.
Bcl-xL promotes the open configuration of the voltage-dependent anion channel and metabolite passage through the outer mitochondrial membrane 总被引:14,自引:0,他引:14
Vander Heiden MG Li XX Gottleib E Hill RB Thompson CB Colombini M 《The Journal of biological chemistry》2001,276(22):19414-19419
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-x(L) 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-x(L) ion channels. Instead, recombinant Bcl-x(L) maintains the outer mitochondrial membrane channel, VDAC, in an open configuration. Consistent with these findings, when ADP-induced oxidative phosphorylation is limited by exogenous beta-NADH, recombinant Bcl-x(L) can sustain outer mitochondrial membrane permeability to ADP. beta-NADH limits respiration by promoting the closed configuration of VDAC. Together these results demonstrate that following an apoptotic signal, Bcl-x(L) can maintain metabolite exchange across the outer mitochondrial membrane by inhibiting VDAC closure. 相似文献
11.
Bcl-2 family proteins are essential regulators of cell death and exert their primary pro- or antiapoptotic roles at the mitochondrial outer membrane. Previously, pro- and antiapoptotic Bcl-2 proteins have been shown to interact with the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane. VDAC is a 283-residue integral membrane protein that forms an aqueous pore in the outer mitochondrial membrane, through which metabolites and other small molecules pass between the cytosol and intermembrane space. The essential life-sustaining function of VDAC in metabolite trafficking is believed to be regulated by proteins of the Bcl-2 family. The protective role of antiapoptotic Bcl-xL may be through its interaction with VDAC. Here, VDAC has been expressed, purified, and refolded into a functional form amenable to NMR studies. Various biophysical experiments indicate that micelle-bound VDAC is in intermediate exchange between monomer and trimer. Using NMR spectroscopy, gel filtration, and chemical cross-linking, we obtained direct evidence for binding of Bcl-xL to VDAC in a detergent micelle system. The VDAC-interacting region of Bcl-xL was characterized by NMR with chemical shift perturbation and transferred cross-saturation. The interaction region was mapped to a putative helical hairpin motif of Bcl-xL that was found to insert into detergent micelles. Our results suggest that Bcl-xL can bind to one or two VDAC molecules forming heterodimers and heterotrimers. Our characterization of the VDAC/Bcl-xL complex offers initial structural insight into the role of antiapoptotic Bcl-xL in regulating apoptotic events in the mitochondrial outer membrane. 相似文献
12.
The voltage-dependent anion channel: an essential player in apoptosis 总被引:12,自引:0,他引:12
The increase of outer mitochondrial membrane permeability is a central event in apoptotic cell death, since it releases several apoptogenic factors such as cytochrome c into the cytoplasm that activate the downstream destructive processes. The voltage-dependent anion channel (VDAC or mitochondrial porin) plays an essential role in the increase of mitochondrial membrane permeability, and it is regulated by the Bcl-2 family of proteins via direct interaction. Anti-apoptotic Bcl-2 family members close the VDAC, whereas some (but not all) pro-apoptotic members interact with the VDAC to generate a protein-conducting channel through which cytochrome c can pass. Although the VDAC is directly involved in the apoptotic increase of mitochondrial membrane permeability and is known to be a component of the permeability transition pore complex, its role in the regulation of outer membrane permeability can be separated from the occurrence of permeability transition events, such as mitochondrial swelling followed by rupture of the outer mitochondrial membrane. The VDAC not only interacts with Bcl-2 family members, but also with other proteins, and probably acts as a convergence point for a variety of life-or-death signals. 相似文献
13.
Marco Colombini 《The Journal of membrane biology》1980,53(2):79-84
Summary A triton X100 extract of mitochondria, isolated from a wall-less mutant ofNeurospora crassa, can be used to insert channels into planar lipid bilayers. These channels have the same properties as the VDAC channels previously reported (Colombini, 1979,Nature (London)
279:643) in the outer membrane of rat liver mitochondria. When large multiwalled liposomes are produced from mixtures of phospholipids andN. crassa mitochondrial membrane material, these liposomes are now permeable to nonelectrolytes up to the size of polyethylene glycol of 3400 mol wt. This yields an estimated radius for the channels inserted into the liposomes of 20 Å.It is proposed that VDAC is the channel which allows the outer mitochondrial membrane to be permeable to small molecules and that this channel has a pore size of 20 Å in radius. 相似文献
14.
Large scale rearrangement of protein domains is associated with voltage gating of the VDAC channel.
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The VDAC channel of the mitochondrial outer membrane is voltage-gated like the larger, more complex voltage-gated channels of the plasma membrane. However, VDAC is a low molecular weight (30 kDa), abundant protein, which is readily purified and reconstituted, making it an ideal system for analyzing the molecular basis for ion selectivity and voltage-gating. We have probed the VDAC channel by subjecting the cloned yeast (S. cerevisiae) VDAC gene to site-directed mutagenesis and introducing the resulting mutant channels into planar bilayers to detect the effects of specific sequence changes on channel properties. This approach has allowed us to formulate and test a model of the open state structure of the VDAC channel. Now we have applied the same approach to analyzing the structure of the channel's low-conducting "closed state" (essentially closed to important metabolites). We have identified protein domains forming the wall of the closed conformation and domains that seem to be removed from the wall of the pore during channel closure. The latter can explain the reduction in pore diameter and volume and the dramatically altered channel selectivity resulting from the channel closure. This process would make a natural coupling between motion of the sensor and channel gating. 相似文献
15.
线粒体电压依赖性阴离子通道及其调控功能 总被引:1,自引:0,他引:1
电压依赖性阴离子通道(voltage-dependent anion channel,VDAC)是存在于线粒体外膜上的31kDa膜蛋白,能在膜上形成亲水性通道,调控阴离子、阳离子、ATP以及其他代谢物进出线粒体,在调节细胞代谢、维持胞内钙稳态,调节细胞凋亡和坏死等过程中发挥重要功能。现就VDAC的结构、特性、活性调节及对细胞功能的调控作一综述。 相似文献
16.
Voltage gating of VDAC is regulated by nonlamellar lipids of mitochondrial membranes 总被引:1,自引:0,他引:1
Rostovtseva TK Kazemi N Weinrich M Bezrukov SM 《The Journal of biological chemistry》2006,281(49):37496-37506
Evidence is accumulating that lipids play important roles in permeabilization of the mitochondria outer membrane (MOM) at the early stage of apoptosis. Lamellar phosphatidylcholine (PC) and nonlamellar phosphatidylethanolamine (PE) lipids are the major membrane components of the MOM. Cardiolipin (CL), the characteristic lipid from the mitochondrial inner membrane, is another nonlamellar lipid recently shown to play a role in MOM permeabilization. We investigate the effect of these three key lipids on the gating properties of the voltage-dependent anion channel (VDAC), the major channel in MOM. We find that PE induces voltage asymmetry in VDAC current-voltage characteristics by promoting channel closure at cis negative applied potentials. Significant asymmetry is also induced by CL. The observed differences in VDAC behavior in PC and PE membranes cannot be explained by differences in the insertion orientation of VDAC in these membranes. Rather, it is clear that the two nonlamellar lipids affect VDAC gating. Using gramicidin A channels as a tool to probe bilayer mechanics, we show that VDAC channels are much more sensitive to the presence of CL than could be expected from the experiments with gramicidin channels. We suggest that this is due to the preferential insertion of VDAC into CL-rich domains. We propose that the specific lipid composition of the mitochondria outer membrane and/or of contact sites might influence MOM permeability by regulating VDAC gating. 相似文献
17.
The mitochondrial outer membrane channel, VDAC, is regulated by a synthetic polyanion 总被引:9,自引:0,他引:9
A synthetic polyanion has been found to modulate the properties of the mitochondrial outer membrane channel, VDAC. This 10 kDa polyanion, first synthesized and described by Konig and co-workers, is a 1:2:3 copolymer of methacrylate, maleate, and styrene. It had been shown to interfere with the access of metabolites to the mitochondrial inner spaces. Here we show that, at nanomolar levels, the polyanion increases the voltage dependence of VDAC channels over 5-fold. Some channels seem to be totally blocked while others display the higher voltage dependence and are able to close at very low membrane potentials (5 mV). At 27 micrograms/ml polyanion, VDAC channels are closed while inserted into liposomes in the absence of any applied potential. The closed state of VDAC induced by the polyanion has similar properties to the closed state induced by elevated membrane potentials. The physical size of the polyanion-induced closed state (in VDAC-containing liposomes) is about 0.9 nm in radius. How this estimate fits with estimates of the channel's open state and estimated volume changes between the open and closed states, is discussed. 相似文献
18.
Kathleen W. Kinnally Pablo M. PeixotoShin-Young Ryu Laurent M. Dejean 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2011,1813(4):616-622
Permeabilization of the mitochondrial membranes is a crucial step in apoptosis and necrosis. This phenomenon allows the release of mitochondrial death factors, which trigger or facilitate different signaling cascades ultimately causing the execution of the cell. The mitochondrial permeability transition pore (mPTP) has long been known as one of the main regulators of mitochondria during cell death. mPTP opening can lead to matrix swelling, subsequent rupture of the outer membrane, and a nonspecific release of intermembrane space proteins into the cytosol. While mPTP was purportedly associated with early apoptosis, recent observations suggest that mitochondrial permeabilization mediated by mPTP is generally more closely linked to events of late apoptosis and necrosis. Mechanisms of mitochondrial membrane permeabilization during cell death, involving three different mitochondrial channels, have been postulated. These include the mPTP in the inner membrane, and the mitochondrial apoptosis-induced channel (MAC) and voltage-dependent anion-selective channel (VDAC) in the outer membrane. New developments on mPTP structure and function, and the involvement of mPTP, MAC, and VDAC in permeabilization of mitochondrial membranes during cell death are explored. This article is part of a Special Issue entitled Mitochondria: the deadly organelle. 相似文献
19.
Lemasters JJ Holmuhamedov EL Czerny C Zhong Z Maldonado EN 《Biochimica et biophysica acta》2012,1818(6):1536-1544
Voltage dependent anion channels (VDAC) are highly conserved proteins that are responsible for permeability of the mitochondrial outer membrane to hydrophilic metabolites like ATP, ADP and respiratory substrates. Although previously assumed to remain open, VDAC closure is emerging as an important mechanism for regulation of global mitochondrial metabolism in apoptotic cells and also in cells that are not dying. During hepatic ethanol oxidation to acetaldehyde, VDAC closure suppresses exchange of mitochondrial metabolites, resulting in inhibition of ureagenesis. In vivo, VDAC closure after ethanol occurs coordinately with mitochondrial uncoupling. Since acetaldehyde passes through membranes independently of channels and transporters, VDAC closure and uncoupling together foster selective and more rapid oxidative metabolism of toxic acetaldehyde to nontoxic acetate by mitochondrial aldehyde dehydrogenase. In single reconstituted VDAC, tubulin decreases VDAC conductance, and in HepG2 hepatoma cells, free tubulin negatively modulates mitochondrial membrane potential, an effect enhanced by protein kinase A. Tubulin-dependent closure of VDAC in cancer cells contributes to suppression of mitochondrial metabolism and may underlie the Warburg phenomenon of aerobic glycolysis. This article is part of a Special Issue entitled: VDAC structure, function, and regulation of mitochondrial metabolism. 相似文献
20.
Conformational change in the mitochondrial channel, VDAC, detected by electron cryo-microscopy. 总被引:1,自引:0,他引:1
Crystalline arrays of the voltage-dependent channel, VDAC, can be produced by treatment of Neurospora mitochondrial outer membranes with phospholipase A2. The membrane crystals undergo a lateral phase transition (lattice contraction) that can be induced by an amphipathic polyanion, which also reduces the channel's gating potential. Electron cryo-microscopy of frozen-hydrated crystals indicates that the mean projected diameters of the channels do not decrease with lattice contraction. Instead, contraction is associated with the disappearance of lateral protein "arms" that normally extend between the channels. A model is presented that explains the changes in channel packing and gating potential in terms of a conformational change involving the movement of a protein "arm" between the bilayer and the channel. 相似文献