電位依存性アニオンチャネル

WordNet

direct the flow of; "channel information towards a broad audience" (同)canalize, canalise
a television station and its programs; "a satellite TV channel"; "surfing through the channels"; "they offer more than one hundred channels" (同)television channel, TV channel
a passage for water (or other fluids) to flow through; "the fields were crossed with irrigation channels"; "gutters carried off the rainwater into a series of channels under the street"
(often plural) a means of communication or access; "it must go through official channels"; "lines of communication were set up between the two firms" (同)communication channel, line
a path over which electrical signals can pass; "a channel is typically what you rent from a telephone company" (同)transmission channel
a deep and relatively narrow body of water (as in a river or a harbor or a strait linking two larger bodies) that allows the best passage for vessels; "the ship went aground in the channel"
relying on or requiring a person or thing for support, supply, or what is needed; "dependent children"; "dependent on moisture"
addicted to a drug (同)dependant, drug-addicted, hooked, strung-out
contingent on something else (同)dependant, qualified
(of a clause) unable to stand alone syntactically as a complete sentence; "a subordinate (or dependent) clause functions as a noun or adjective or adverb within a sentence" (同)subordinate
the rate at which energy is drawn from a source that produces a flow of electricity in a circuit; expressed in volts (同)electromotive_force, emf
a negatively charged ion
official routes of communication; "you have to go through channels"

PrepTutorEJDIC

〈C〉『水路』(川・湾・運河の船の通行ができる深い部分) / 〈U〉河床・川底 / 〈C〉『海峡』 / 〈C〉みぞ(groove),(道路の)水渠(すいきょ) / 《複数形で》(運搬・伝達の)正式の経路(手続き);(一般に)経路 / 〈C〉(テレビ・ラジオの)チャンネル / …‘に'水路を開く / …‘に'みぞを堀る / …'を'伝える,流す
『頼っている』,依存している,従属している / 扶養される人(家族)
電圧,電圧量,ボルト数
陰イオン

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/01/29 15:15:20」(JST)

wiki en

Crystal Structure of the Human Voltage-Dependent Anion Channel. The arrows denote the antiparallel beta sheets that form the characteristic beta-barrel

Voltage-dependent anion channels are a class of porin ion channel located on the outer mitochondrial membrane.^[1] There is debate as to whether or not this channel is expressed in the cell surface membrane.^[2] ^[3]^[4]

This major protein of the outer mitochondrial membrane of eukaryotes forms a voltage-dependent anion-selective channel (VDAC) that behaves as a general diffusion pore for small hydrophilic molecules.^[5]^[6]^[7]^[8] The channel adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. VDAC facilitates the exchange of ions and molecules between mitochondria and cytosol and is regulated by the interactions with other proteins and small molecules.^[9]

Structure

This protein contains about 280 amino acids and forms a beta barrel which spans span the mitochondrial outer membrane.^[10]^[11]

Since its discovery in 1976, extensive function and structure analysis of VDAC proteins has been conducted. A prominent feature of the pore emerged: when reconstituted into planar lipid bilayers, there is a voltage-dependent switch between an anion-selective high-conductance state with high metabolite flux and a cation-selective low-conductance state with limited passage of metabolites.

More than 30 years after its initial discovery, in 2008, three independent structural projects of VDAC-1 were completed. The first was solved by multi-dimensional NMR spectroscopy. The second applied a hybrid approach using crystallographic data. The third was for mouse VDAC-1 crystals determined by X-ray crystallographic techniques. The three projects of the 3D structures of VDAC-1 revealed many structural features. First, VDAC-1 represents a new structural class of outer membrane β-barrel proteins with an odd number of strands. Another aspect is that the negatively charged side chain of residue E73 is oriented towards the hydrophobic membrane environment. The 19-stranded 3D structure obtained under different experimental sources by three different laboratories fits the EM and AFM data from native membrane sources and represents a biologically relevant state of VDAC-1.^[9]

Mechanism

At membrane potentials exceeding 30 mV (positive or negative), VDAC assumes a closed state, and transitions to its open state once the voltage drops below this threshold. Although both states allow passage of simple salts, VDAC is much more stringent with organic anions, a category into which most metabolites fall. ^[12] The precise mechanism for coupling voltage changes to conformational changes within the protein has not yet been worked out, but studies by Thomas et al. suggest that when the protein transitions to the closed form, voltage changes lead to the removal of a large section of the protein from the channel and decrease effective pore radius. ^[13] Several lysine residues, as well as Glu-152, have been implicated as especially important sensor residues within the protein. ^[14]

Biological Function

The voltage-dependent ion channel plays a key role in regulating metabolic and energetic flux across the outer mitochondrial membrane. It is involved in the transport of ATP, ADP, pyruvate, malate, and other metabolites, and thus communicates extensively with enzymes from metabolic pathways. ^[12] The ATP-dependent cytosolic enzymes hexokinase, glucokinase, and glycerol kinase, as well as the mitochondrial enzyme creatine kinase, have all been found to bind to VDAC. This binding puts them in close proximity to ATP released from the mitochondria. In particular, the binding of hexokinase is presumed to play a key role in coupling glycolysis to oxidative phosphorylation. ^[13] Additionally, VDAC is an important regulator of Ca²⁺ transport in and out of the mitochondria. Because Ca²⁺ is a cofactor for metabolic enzymes such as pyruvate dehydrogenase and isocitrate dehydrogenase, energetic production and homeostasis are both affected by VDAC’s permeability to Ca²⁺. ^[15]

Disease Relevance

VDAC has also been shown to play a role in apoptosis. ^[16] During apoptosis, increased permeability of VDAC allows for the release of apoptogenic factors such as cytochrome c. Although cyt. c plays an essential role in oxidative phosphorylation within the mitochondrion, in the cytosol it activates proteolytic enzymes called caspases, which play a major role in cell death.^[17] Although the mechanism for VDAC-facilitated cyt. c release has not yet been fully elucidated, some research suggests that oligomerization between individual subunits may create a large flexible pore through which cyt. c can pass.^[18]A more important factor is that release of cyt c. is also regulated by the Bcl-2 protein family: Bax interacts directly with VDAC to increase pore size and promote cyt. c release, while anti-apoptotic Bcl-xL produces the exact opposite effect.^[19] In fact, it has been shown that antibodies that inhibit VDAC also interfere with Bax-mediated cyt. c release in both isolated mitchondria and whole cells.^[20] This key role in apoptosis suggests VDAC as a potential target for chemotherapeutic drugs.

Examples

Yeast contains two members of this family (genes POR1 and POR2); vertebrates have at least three members (genes VDAC1, VDAC2 and VDAC3).^[10]

Humans, like most higher eukaryotes, encode three different VDACs; VDAC1, VDAC2, and VDAC3. Together with TOMM40 and TOMM40L they represent a family of evolutionarily related β-barrels.^[21]

Plants have the largest number of VDACs. Arabidopsis encode four different VDACs but this number can be larger in other species.^[22]

References

^ Hoogenboom BW, Suda K, Engel A, Fotiadis D (2007). "The supramolecular assemblies of voltage-dependent anion channels in the native membrane". J. Mol. Biol. 370 (2): 246–55. doi:10.1016/j.jmb.2007.04.073. PMID 17524423.
^ Sabirov, R. Z.; Merzlyak, P. G. (2012). "Plasmalemmal VDAC controversies and maxi-anion channel puzzle". Biochimica et Biophysica Acta (BBA) - Biomembranes 1818 (6): 1570. doi:10.1016/j.bbamem.2011.09.024. edit
^ De Pinto, V.; Messina, A.; Lane, D. J. R.; Lawen, A. (2010). "Voltage-dependent anion-selective channel (VDAC) in the plasma membrane". FEBS Letters 584 (9): 1793–1799. doi:10.1016/j.febslet.2010.02.049. PMID 20184885. edit
^ Niehage, C.; Steenblock, C.; Pursche, T.; Bornhäuser, M.; Corbeil, D.; Hoflack, B. (2011). Borlongan, Cesario V, ed. "The Cell Surface Proteome of Human Mesenchymal Stromal Cells". PLoS ONE 6 (5): e20399. doi:10.1371/journal.pone.0020399. PMC 3102717. PMID 21637820. edit
^ Benz R (1994). "Permeation of hydrophilic solutes through mitochondrial outer membranes: review on mitochondrial porins". Biochim. Biophys. Acta 1197 (2): 167–196. doi:10.1016/0304-4157(94)90004-3. PMID 8031826.
^ Mannella CA (1992). "The 'ins' and 'outs' of mitochondrial membrane channels". Trends Biochem. Sci. 17 (8): 315–320. doi:10.1016/0968-0004(92)90444-E. PMID 1384178.
^ Dihanich M (1990). "The biogenesis and function of eukaryotic porins". Experientia 46 (2): 146–153. doi:10.1007/BF02027310. PMID 1689252.
^ Forte M, Guy HR, Mannella CA (1987). "Molecular genetics of the VDAC ion channel: structural model and sequence analysis". J. Bioenerg. Biomembr. 19 (4): 341–350. doi:10.1007/BF00768537. PMID 2442148.
^ ^a ^b Hiller S, Abramson J, Mannella C, Wagner G, Zeth K (September 2010). "The 3D structures of VDAC represent a native conformation". Trends Biochem. Sci. 35 (9): 514–21. doi:10.1016/j.tibs.2010.03.005. PMC 2933295. PMID 20708406.
^ ^a ^b Sampson MJ, Lovell RS, Davison DB, Craigen WJ (1996). "A novel mouse mitochondrial voltage-dependent anion channel gene localizes to chromosome 8". Genomics 36 (1): 192–196. doi:10.1006/geno.1996.0445. PMID 8812436.
^ Zeth K (2010). "Structure and evolution of mitochondrial outer membrane proteins of beta-barrel topology". Biochim. Biophys. Acta 1797 (6–7): 1292–9. doi:10.1016/j.bbabio.2010.04.019. PMID 20450883.
^ ^a ^b Blachly-Dyson, E. and Forte, M. (2001). "VDAC Channels". IUBMB Life 52 (3-5): 113–18. doi:10.1080/15216540152845902. PMID 11798022.
^ ^a ^b Colombini, M., Blachly-Dyson, E., Forte, M. (1996). "VDAC, a channel in the outer mitochondrial membrane". Ion Channels 4: 162–209. PMID 8744209.
^ Colombini, M., Blachly-Dyson, E., Forte, M. (1993). "Mapping of residues forming the voltage sensor of the voltage-dependent anion-selective channel". Proc. Natl. Acad. Sci. USA 90 (12): 5446–49. doi:10.1073/pnas.90.12.5446. PMC 46737. PMID 7685903.
^ Shoshan-Barmatz V, Gincel D. (2003). "The voltage-dependent anion channel: characterization, modulation, and role in mitochondrial function in cell life and death.". Cell Biochem. Biophys. 39 (3): 279–92. doi:10.1385/CBB:39:3:279. PMID 14716081.
^ Lemasters JJ, Holmuhamedov E. (2006). "Voltage-dependent anion channel (VDAC) as mitochondrial governator--thinking outside the box.". Biochim. Biophys. Acta. 1762 (2): 181–90. doi:10.1016/j.bbadis.2005.10.006. PMID 16307870.
^ Tsujimoto Y, Shimizu S. (2002). "The voltage-dependent anion channel: an essential player in apoptosis.". Biochimie 84 (2-3): 187–93. doi:10.1016/S0300-9084(02)01370-6. PMID 12022949.
^ Zalk R, Israelson A, Garty ES, Azoulay-Zohar H, Shoshan-Barmatz V. (2005). "Oligomeric states of the voltage-dependent anion channel and cytochrome c release from mitochondria". Biochem J. 386 (1): 73–83. doi:10.1042/BJ20041356. PMID 15456403.
^ Shimizu S, Narita M, Tsujimoto Y. (1999). "Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC". Nature 399 (6735): 483–7. doi:10.1038/20959. PMID 10365962.
^ Shimizu S, Matsuoka Y, Shinohara Y, Yoneda Y, Tsujimoto Y. (2001). "Essential role of voltage-dependent anion channel in various forms of apoptosis in mammalian cells.". J. Cell Biol. 152 (2): 237–50. doi:10.1083/jcb.152.2.237. PMID 11266442.
^ Bay DC, Hafez M, Young MJ, Court DA (June 2012). "Phylogenetic and coevolutionary analysis of the β-barrel protein family comprised of mitochondrial porin (VDAC) and Tom40". Biochim. Biophys. Acta 1818 (6): 1502–19. doi:10.1016/j.bbamem.2011.11.027. PMID 22178864.
^ Homblé F, Krammer E, Prevost M (June 2012). "Plant VDAC: facts and speculations.". Biochim. Biophys. Acta 1818 (6): 1486–501. doi:10.1016/j.bbamem.2011.11.028. PMID 22155681.

External links

Voltage-Dependent Anion Channels at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the public domain Pfam and InterPro IPR001925

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 赤血球水分量の制御 control of red blood cell hydration
2. 成人における高カリウム血症の原因および評価 causes and evaluation of hyperkalemia in adults
3. 抗てんかん剤の薬理学 pharmacology of antiepileptic drugs
4. Lambert-Eaton筋無力症候群の臨床的特徴および診断 clinical features and diagnosis of lambert eaton myasthenic syndrome
5. 心筋活動電位および抗不整脈剤の作用 myocardial action potential and action of antiarrhythmic drugs

English Journal

VDAC1-interacting anion transport inhibitors inhibit VDAC1 oligomerization and apoptosis.

Ben-Hail D1, Shoshan-Barmatz V2.
Biochimica et biophysica acta.Biochim Biophys Acta.2016 Jul;1863(7 Pt A):1612-23. doi: 10.1016/j.bbamcr.2016.04.002. Epub 2016 Apr 8.
Mitochondria-mediated apoptosis involves pro-apoptotic protein release from the mitochondria to the cytosol, triggering apoptosis. However, the mechanisms by which apoptotic initiators cross the outer mitochondrial membrane (OMM) remain unclear. The voltage-dependent anion channel 1 (VDAC1), an OMM
PMID 27064145

Effect of Moderate Exercise on Mitochondrial Proteome in Heart Tissue of Spontaneous Hypertensive Rats.

Rocha LA1, Oliveira KS2, Migliolo L2, Franco OL3.
American journal of hypertension.Am J Hypertens.2016 Jun;29(6):696-704. doi: 10.1093/ajh/hpv160. Epub 2015 Sep 21.
BACKGROUND: Hypertension is a multifactorial disease and an important independent risk factor for cardiovascular diseases. Exercise training is one of the most important non-pharmacological therapeutic strategies for treating hypertension; however, mitochondrial adaptations in the hypertensive heart
PMID 26391256

The N-terminus of VDAC: Structure, mutational analysis, and a potential role in regulating barrel shape.

Shuvo SR1, Ferens FG1, Court DA2.
Biochimica et biophysica acta.Biochim Biophys Acta.2016 Jun;1858(6):1350-61. doi: 10.1016/j.bbamem.2016.03.017. Epub 2016 Mar 18.
A novel feature of the voltage-dependent anion channel (VDAC, mitochondrial porin), is the barrel, comprising an odd number of β-strands and closed by parallel strands. Recent research has focused on the N-terminal segment, which in the available structures, resides in the lumen and is not part of
PMID 26997586

Japanese Journal

Drug Development Targeting the Glycogen Synthase Kinase-3β (GSK-3β)-Mediated Signal Transduction Pathway : Role of GSK-3β in Myocardial Protection Against Ischemia/Reperfusion Injury

MIURA Tetsuji,NISHIHARA Masahiro,MIKI Takayuki
Journal of pharmacological sciences 109(2), 162-167, 2009-02-20
… The mPTP primarily consists of adenine nucleotide translocator (ANT) and voltage-dependent anion channel, and its opening is triggered by binding of cyclophilin-D (CyP-D) to ANT, which increases Ca2+ sensitivity of the mPTP. …
NAID 10025734088

Bioreductive activation of quinone antitumor drugs by mitochondrial voltage-dependent anion channel 1

SIMAMURA Eriko,SHIMADA Hiroki,ISHIGAKI Yasuhito,HATTA Toshihisa,HIGASHI Nobuaki,HIRAI Kei-Ichi
Anatomical science international 83(4), 261-266, 2008-12-01
NAID 10025130377

Related Pictures

★リンクテーブル★

リンク元	「電位依存性アニオンチャネル」
拡張検索	「voltage-dependent anion channel 1」「voltage-dependent anion channel 2」
関連記事	「channel」「dependent」「voltage」「anion channel」「ani」

「電位依存性アニオンチャネル」

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Eukaryotic porin
Identifiers
Symbol	Porin_3
Pfam	PF01459
InterPro	IPR001925
PROSITE	PDOC00483
TCDB	1.B.8
OPM superfamily	210
OPM protein	3emn
CDD	cd07306
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary