電位依存性アニオンチャネル1

関: voltage-dependent anion channel 1

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/06/20 19:00:30」(JST)

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Voltage-dependent anion-selective channel protein 1 is a protein that in humans is encoded by the VDAC1 gene on chromosome 5.^[1]^[2] This protein is a voltage-dependent anion channel and shares high structural homology with the other VDAC isoforms, which are involved in the regulation of cell metabolism, mitochondrial apoptosis, and spermatogenesis.^[3]^[4]^[5]^[6] In particular, VDAC1 is the major calcium ion transport channel and is implicated in cancer and Parkinson’s Disease (PD).^[7]^[8]

Structure

The three VDAC isoforms in human are highly conserved, particularly with respect to their 3D structure. VDACs form a wide β-barrel structure, inside of which the N-terminal resides to partially close the pore.^[9] For VDAC1, this barrel-like channel is composed of 19 amphipathic β-strands, and the end of the N-terminal contains α-helix segments. The N-terminal is proposed to as a gate to the pore via swinging motions facilitated by a short glycine-containing motif. Additionally, the N-terminal serves as a docking site for HK1 binding.^[10]

Function

VDAC1 belongs to the mitochondrial porin family and is expected to share similar biological functions to the other VDAC isoforms.^[11] Of the three isoforms, VDAC1 is the main calcium ion transport channel and the most abundantly transcribed.^[8]^[12] VDACs are involved in cell metabolism by transporting ATP and other small metabolites across the outer mitochondrial membrane (OMM). Of note, its role in transporting calcium ions allows the protein to regulate the TCA cycle and, by extension, reactive oxygen species (ROS) production.^[7] In yeast cells, ROS accumulates in response to oxidative stress, which results in impaired mitochondrial function and a “petite” phenotype. However, petite yeast cells exhibit a longer lifespan than wildtype cells and indicate a protective function by VDAC1 in similar circumstances, such as aging.^[10]^[12] In addition, VDACs form part of the mitochondrial permeability transition pore (MPTP) and, thus, facilitate cytochrome C release, leading to apoptosis. VDACs have also been observed to interact with pro- or antiapoptotic proteins, such as Bcl-2 family proteins and kinases, and so may contribute to apoptosis independently from the MPTP.^[11]

Clinical Significance

VDAC1 has been implicated in cancer through its interactions with antiapoptotic Bcl-2 proteins, particularly Bcl-xl, and Mcl-1, which are overexpressed during cancer. These two Bcl-2 proteins interact with VDAC1 to regulate calcium ion transport across the OMM and, ultimately, ROS production. While high levels of ROS induce cell death, non-lethal levels interfere with signal transduction pathways that can then promote cell proliferation, migration, and invasion in cancer cells.^[7] Moreover, VDAC1 overexpression has been associated with increased apoptotic response and anti-cancer drugs and treatment efficacy, further supporting VDAC1 as a therapeutic target for cancer treatment.^[7]^[13]

VDAC1 function in calcium ion transport also involves the protein in neurodegenerative diseases. In PD, VDAC1 increases calcium ion levels within the mitochondria, resulting in increased mitochondrial permeability, disrupted mitochondrial membrane potential, elevated ROS production, cell death, and neuronal degeneration.^[8]

Interactions

VDAC1 has been shown to interact with:

BCL2-like 1,^[14]^[15]^[16]^[17]
Bcl-2-associated X protein,^[14]^[15]
DYNLT3,^[18]
Gelsolin,^[19]
PRKCE,^[20]
HK1^[10]
Parkin^[21]
eNOS^[4]
Mcl-1^[7]
HK^[13]

References

^ Blachly-Dyson E, Baldini A, Litt M, McCabe ER, Forte M (July 1994). "Human genes encoding the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane: mapping and identification of two new isoforms". Genomics 20 (1): 62–7. doi:10.1006/geno.1994.1127. PMID 7517385.
^ "Entrez Gene: VDAC1 voltage-dependent anion channel 1".
^ Subedi KP, Kim JC, Kang M, Son MJ, Kim YS, Woo SH (Feb 2011). "Voltage-dependent anion channel 2 modulates resting Ca²+ sparks, but not action potential-induced Ca²+ signaling in cardiac myocytes". Cell Calcium 49 (2): 136–43. doi:10.1016/j.ceca.2010.12.004. PMID 21241999.
^ ^a ^b Alvira CM, Umesh A, Husted C, Ying L, Hou Y, Lyu SC, Nowak J, Cornfield DN (Nov 2012). "Voltage-dependent anion channel-2 interaction with nitric oxide synthase enhances pulmonary artery endothelial cell nitric oxide production". American Journal of Respiratory Cell and Molecular Biology 47 (5): 669–78. doi:10.1165/rcmb.2011-0436OC. PMID 22842492.
^ Cheng EH, Sheiko TV, Fisher JK, Craigen WJ, Korsmeyer SJ (Jul 2003). "VDAC2 inhibits BAK activation and mitochondrial apoptosis". Science 301 (5632): 513–7. doi:10.1126/science.1083995. PMID 12881569.
^ Li Z, Wang Y, Xue Y, Li X, Cao H, Zheng SJ (Feb 2012). "Critical role for voltage-dependent anion channel 2 in infectious bursal disease virus-induced apoptosis in host cells via interaction with VP5". Journal of Virology 86 (3): 1328–38. doi:10.1128/JVI.06104-11. PMID 22114330.
^ ^a ^b ^c ^d ^e Huang H, Shah K, Bradbury NA, Li C, White C (23 October 2014). "Mcl-1 promotes lung cancer cell migration by directly interacting with VDAC to increase mitochondrial Ca2+ uptake and reactive oxygen species generation". Cell Death & Disease 5: e1482. doi:10.1038/cddis.2014.419. PMID 25341036.
^ ^a ^b ^c Chu Y, Goldman JG, Kelly L, He Y, Waliczek T, Kordower JH (Sep 2014). "Abnormal alpha-synuclein reduces nigral voltage-dependent anion channel 1 in sporadic and experimental Parkinson's disease". Neurobiology of Disease 69: 1–14. doi:10.1016/j.nbd.2014.05.003. PMID 24825319.
^ Amodeo GF, Scorciapino MA, Messina A, De Pinto V, Ceccarelli M (2014). "Charged residues distribution modulates selectivity of the open state of human isoforms of the voltage dependent anion-selective channel". PLOS ONE 9 (8): e103879. doi:10.1371/journal.pone.0103879. PMID 25084457.
^ ^a ^b ^c Reina S, Palermo V, Guarnera A, Guarino F, Messina A, Mazzoni C, De Pinto V (Jul 2010). "Swapping of the N-terminus of VDAC1 with VDAC3 restores full activity of the channel and confers anti-aging features to the cell". FEBS Letters 584 (13): 2837–44. doi:10.1016/j.febslet.2010.04.066. PMID 20434446.
^ ^a ^b Lee MJ, Kim JY, Suk K, Park JH (May 2004). "Identification of the hypoxia-inducible factor 1 alpha-responsive HGTD-P gene as a mediator in the mitochondrial apoptotic pathway". Molecular and Cellular Biology 24 (9): 3918–27. doi:10.1128/mcb.24.9.3918-3927.2004. PMID 15082785.
^ ^a ^b De Pinto V, Guarino F, Guarnera A, Messina A, Reina S, Tomasello FM, Palermo V, Mazzoni C (2010). "Characterization of human VDAC isoforms: a peculiar function for VDAC3?". Biochimica et Biophysica Acta 1797 (6-7): 1268–75. doi:10.1016/j.bbabio.2010.01.031. PMID 20138821.
^ ^a ^b Weisthal S, Keinan N, Ben-Hail D, Arif T, Shoshan-Barmatz V (Oct 2014). "Ca(2+)-mediated regulation of VDAC1 expression levels is associated with cell death induction". Biochimica et Biophysica Acta 1843 (10): 2270–81. doi:10.1016/j.bbamcr.2014.03.021. PMID 24704533.
^ ^a ^b Weng C, Li Y, Xu D, Shi Y, Tang H (March 2005). "Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells". J. Biol. Chem. 280 (11): 10491–500. doi:10.1074/jbc.M412819200. PMID 15637055.
^ ^a ^b Shi Y, Chen J, Weng C, Chen R, Zheng Y, Chen Q, Tang H (June 2003). "Identification of the protein-protein contact site and interaction mode of human VDAC1 with Bcl-2 family proteins". Biochem. Biophys. Res. Commun. 305 (4): 989–96. doi:10.1016/s0006-291x(03)00871-4. PMID 12767928.
^ Shimizu S, Konishi A, Kodama T, Tsujimoto Y (March 2000). "BH4 domain of antiapoptotic Bcl-2 family members closes voltage-dependent anion channel and inhibits apoptotic mitochondrial changes and cell death". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3100–5. doi:10.1073/pnas.97.7.3100. PMC 16199. PMID 10737788.
^ Shimizu S, Narita M, Tsujimoto Y (June 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.
^ Schwarzer C, Barnikol-Watanabe S, Thinnes FP, Hilschmann N (September 2002). "Voltage-dependent anion-selective channel (VDAC) interacts with the dynein light chain Tctex1 and the heat-shock protein PBP74". Int. J. Biochem. Cell Biol. 34 (9): 1059–70. doi:10.1016/s1357-2725(02)00026-2. PMID 12009301.
^ Kusano H, Shimizu S, Koya RC, Fujita H, Kamada S, Kuzumaki N, Tsujimoto Y (October 2000). "Human gelsolin prevents apoptosis by inhibiting apoptotic mitochondrial changes via closing VDAC". Oncogene 19 (42): 4807–14. doi:10.1038/sj.onc.1203868. PMID 11039896.
^ Baines CP, Song CX, Zheng YT, Wang GW, Zhang J, Wang OL, Guo Y, Bolli R, Cardwell EM, Ping P (May 2003). "Protein kinase Cepsilon interacts with and inhibits the permeability transition pore in cardiac mitochondria". Circ. Res. 92 (8): 873–80. doi:10.1161/01.RES.0000069215.36389.8D. PMC 3691672. PMID 12663490.
^ Sun Y, Vashisht AA, Tchieu J, Wohlschlegel JA, Dreier L (Nov 2012). "Voltage-dependent anion channels (VDACs) recruit Parkin to defective mitochondria to promote mitochondrial autophagy". The Journal of Biological Chemistry 287 (48): 40652–60. doi:10.1074/jbc.M112.419721. PMID 23060438.

External links

VDAC1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

English Journal

RETRACTED ARTICLE: MAVS protects cells from apoptosis by negatively regulating VDAC1.

Xu Y, Zhong H, Shi W.SourceKey Laboratory for Molecular Enzymology and Engineering, Jilin University, 2519 Jie-Fang Road, 130021, Changchun, China.
Molecular and cellular biochemistry.Mol Cell Biochem.2013 Mar;375(1-2):219. doi: 10.1007/s11010-010-0658-4. Epub 2010 Nov 26.
PMID 21110072

Curcumin prevents mitochondrial dysfunction in the brain of the senescence-accelerated mouse - prone 8.

Eckert GP, Schiborr C, Hagl S, Abdel-Kader R, Müller WE, Rimbach G, Frank J.SourceDepartment of Pharmacology, Biocenter Niederursel, University of Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany. Electronic address: g.p.eckert@em.uni-frankfurt.de.
Neurochemistry international.Neurochem Int.2013 Feb 16. pii: S0197-0186(13)00059-4. doi: 10.1016/j.neuint.2013.02.014. [Epub ahead of print]
The aging brain suffers mitochondrial dysfunction and a reduced availability of energy in the form of ATP, which in turn may cause or promote the decline in cognitive, sensory, and motor function observed with advancing age. There is a need for animal models that display some of the pathological fea
PMID 23422877

Myostatin induces mitochondrial metabolic alteration and typical apoptosis in cancer cells.

Liu Y, Cheng H, Zhou Y, Zhu Y, Bian R, Chen Y, Li C, Ma Q, Zheng Q, Zhang Y, Jin H, Wang X, Chen Q, Zhu D.Source1] The State Key Laboratory of Biomembrane and Membrane Biotechnology, Chinese Academy of Sciences, Beijing, China [2] The Graduate School of Chinese Academy of Sciences, Beijing, China.
Cell death & disease.Cell Death Dis.2013 Feb 14;4:e494. doi: 10.1038/cddis.2013.31.
Myostatin, a member of the transforming growth factor-β superfamily, regulates the glucose metabolism of muscle cells, while dysregulated myostatin activity is associated with a number of metabolic disorders, including muscle cachexia, obesity and type II diabetes. We observed that myostatin induce
PMID 23412387

Japanese Journal

PINK/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1

GEISLER S
Nat. Cell Biol. 12, 119-131, 2010
NAID 80020854923

VDAC1, having a shorter N-terminus than VDAC2 but showing the same migration in an SDS polyacrylamide gel, is the predominant form expressed in mitochondria of various tissues

Yamamoto Takenori,Yamada Akiko,Watanabe Masahiro,Yoshimura Yuya,Yamazaki Naoshi,Yoshimura Yoshiyuki,Yamauchi Takashi,Kataoka Masatoshi,Nagata Toshihiko,Terada Hiroshi,Shinohara Yasuo
JOURNAL OF PROTEOME RESEARCH 5(12), 3336-3344, 2006-00-00
NAID 120004448004

VDAC1 is a transplasma membrane NADH-ferricyanide reductase

BAKER MA
J Biol Chem 279, 4811-4819, 2004
NAID 80016493354

Related Pictures

VDAC1 antibody) at dilution of 1:50 (under The VDAC1 N-terminus is essential both for Protein VDAC1 PDB 2JK4.png / Immunofluorescence - VDAC1 Schematic representation of VDAC1 inserted VDAC1 IHC 55259-1-AP VDAC1 Antibody hVDAC1 Mouse VDAC1 membrane channel protein

★リンクテーブル★

リンク元	「voltage-dependent anion channel 1」「電位依存性アニオンチャネル1」

「voltage-dependent anion channel 1」

VDAC1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2JK4, 2K4T
Identifiers
Aliases	VDAC1, PORIN, VDAC-1, voltage dependent anion channel 1
External IDs	MGI: 106919 HomoloGene: 107244 GeneCards: 7416
Gene ontology
Molecular function	• porin activity; • ion channel binding; • protein complex binding; • anion channel activity; • voltage-gated anion channel activity; • protein binding; • protein kinase binding;
Cellular component	• integral component of membrane; • membrane; • synaptic vesicle; • myelin sheath; • plasma membrane; • protein complex; • mitochondrial outer membrane; • mitochondrion; • mitochondrial inner membrane; • membrane raft; • mitochondrial nucleoid; • extracellular exosome; • pore complex; • nucleus;
Biological process	• chemical synaptic transmission; • epithelial cell differentiation; • mitochondrial calcium ion transport; • macromitophagy; • neuron-neuron synaptic transmission; • ion transport; • learning; • anion transport; • behavioral fear response; • anion transmembrane transport; • regulation of mitophagy; • regulation of anion transmembrane transport; • transmembrane transport; • transport; • negative regulation of reactive oxygen species metabolic process; • viral process; • macroautophagy; • regulation of anion transport; • apoptotic process;
	Sources:Amigo / QuickGO
RNA expression pattern
	; ;
	More reference expression data
Orthologs
	7416
	22333
	ENSG00000213585
	ENSMUSG00000020402
	P21796
	Q60932
	NM_003374
	NM_011694
	NP_003365.1
	NP_035824.1
	Wikidata
View/Edit Human	View/Edit Mouse

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電位依存性アニオンチャネル1

関: VDAC1

「電位依存性アニオンチャネル1」

　　[★]

英: voltage-dependent anion channel 1、VDAC1

[pmid7517385-1] Blachly-Dyson E, Baldini A, Litt M, McCabe ER, Forte M (July 1994). "Human genes encoding the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane: mapping and identification of two new isoforms". Genomics 20 (1): 62–7. doi:10.1006/geno.1994.1127. PMID 7517385.

[entrez-2] "Entrez Gene: VDAC1 voltage-dependent anion channel 1".

[pmid21241999-3] Subedi KP, Kim JC, Kang M, Son MJ, Kim YS, Woo SH (Feb 2011). "Voltage-dependent anion channel 2 modulates resting Ca²+ sparks, but not action potential-induced Ca²+ signaling in cardiac myocytes". Cell Calcium 49 (2): 136–43. doi:10.1016/j.ceca.2010.12.004. PMID 21241999.

[pmid22842492-4] Alvira CM, Umesh A, Husted C, Ying L, Hou Y, Lyu SC, Nowak J, Cornfield DN (Nov 2012). "Voltage-dependent anion channel-2 interaction with nitric oxide synthase enhances pulmonary artery endothelial cell nitric oxide production". American Journal of Respiratory Cell and Molecular Biology 47 (5): 669–78. doi:10.1165/rcmb.2011-0436OC. PMID 22842492.

[pmid12881569-5] Cheng EH, Sheiko TV, Fisher JK, Craigen WJ, Korsmeyer SJ (Jul 2003). "VDAC2 inhibits BAK activation and mitochondrial apoptosis". Science 301 (5632): 513–7. doi:10.1126/science.1083995. PMID 12881569.

[pmid22114330-6] Li Z, Wang Y, Xue Y, Li X, Cao H, Zheng SJ (Feb 2012). "Critical role for voltage-dependent anion channel 2 in infectious bursal disease virus-induced apoptosis in host cells via interaction with VP5". Journal of Virology 86 (3): 1328–38. doi:10.1128/JVI.06104-11. PMID 22114330.

[pmid25341036-7] Huang H, Shah K, Bradbury NA, Li C, White C (23 October 2014). "Mcl-1 promotes lung cancer cell migration by directly interacting with VDAC to increase mitochondrial Ca2+ uptake and reactive oxygen species generation". Cell Death & Disease 5: e1482. doi:10.1038/cddis.2014.419. PMID 25341036.

[pmid24825319-8] Chu Y, Goldman JG, Kelly L, He Y, Waliczek T, Kordower JH (Sep 2014). "Abnormal alpha-synuclein reduces nigral voltage-dependent anion channel 1 in sporadic and experimental Parkinson's disease". Neurobiology of Disease 69: 1–14. doi:10.1016/j.nbd.2014.05.003. PMID 24825319.

[pmid25084457-9] Amodeo GF, Scorciapino MA, Messina A, De Pinto V, Ceccarelli M (2014). "Charged residues distribution modulates selectivity of the open state of human isoforms of the voltage dependent anion-selective channel". PLOS ONE 9 (8): e103879. doi:10.1371/journal.pone.0103879. PMID 25084457.

[pmid20434446-10] Reina S, Palermo V, Guarnera A, Guarino F, Messina A, Mazzoni C, De Pinto V (Jul 2010). "Swapping of the N-terminus of VDAC1 with VDAC3 restores full activity of the channel and confers anti-aging features to the cell". FEBS Letters 584 (13): 2837–44. doi:10.1016/j.febslet.2010.04.066. PMID 20434446.

[pmid15082785-11] Lee MJ, Kim JY, Suk K, Park JH (May 2004). "Identification of the hypoxia-inducible factor 1 alpha-responsive HGTD-P gene as a mediator in the mitochondrial apoptotic pathway". Molecular and Cellular Biology 24 (9): 3918–27. doi:10.1128/mcb.24.9.3918-3927.2004. PMID 15082785.

[pmid20138821-12] De Pinto V, Guarino F, Guarnera A, Messina A, Reina S, Tomasello FM, Palermo V, Mazzoni C (2010). "Characterization of human VDAC isoforms: a peculiar function for VDAC3?". Biochimica et Biophysica Acta 1797 (6-7): 1268–75. doi:10.1016/j.bbabio.2010.01.031. PMID 20138821.

[pmid24704533-13] Weisthal S, Keinan N, Ben-Hail D, Arif T, Shoshan-Barmatz V (Oct 2014). "Ca(2+)-mediated regulation of VDAC1 expression levels is associated with cell death induction". Biochimica et Biophysica Acta 1843 (10): 2270–81. doi:10.1016/j.bbamcr.2014.03.021. PMID 24704533.

[pmid15637055-14] Weng C, Li Y, Xu D, Shi Y, Tang H (March 2005). "Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells". J. Biol. Chem. 280 (11): 10491–500. doi:10.1074/jbc.M412819200. PMID 15637055.

[pmid12767928-15] Shi Y, Chen J, Weng C, Chen R, Zheng Y, Chen Q, Tang H (June 2003). "Identification of the protein-protein contact site and interaction mode of human VDAC1 with Bcl-2 family proteins". Biochem. Biophys. Res. Commun. 305 (4): 989–96. doi:10.1016/s0006-291x(03)00871-4. PMID 12767928.

[pmid10737788-16] Shimizu S, Konishi A, Kodama T, Tsujimoto Y (March 2000). "BH4 domain of antiapoptotic Bcl-2 family members closes voltage-dependent anion channel and inhibits apoptotic mitochondrial changes and cell death". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3100–5. doi:10.1073/pnas.97.7.3100. PMC 16199. PMID 10737788.

[pmid10365962-17] Shimizu S, Narita M, Tsujimoto Y (June 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.

[pmid12009301-18] Schwarzer C, Barnikol-Watanabe S, Thinnes FP, Hilschmann N (September 2002). "Voltage-dependent anion-selective channel (VDAC) interacts with the dynein light chain Tctex1 and the heat-shock protein PBP74". Int. J. Biochem. Cell Biol. 34 (9): 1059–70. doi:10.1016/s1357-2725(02)00026-2. PMID 12009301.

[pmid11039896-19] Kusano H, Shimizu S, Koya RC, Fujita H, Kamada S, Kuzumaki N, Tsujimoto Y (October 2000). "Human gelsolin prevents apoptosis by inhibiting apoptotic mitochondrial changes via closing VDAC". Oncogene 19 (42): 4807–14. doi:10.1038/sj.onc.1203868. PMID 11039896.

[pmid12663490-20] Baines CP, Song CX, Zheng YT, Wang GW, Zhang J, Wang OL, Guo Y, Bolli R, Cardwell EM, Ping P (May 2003). "Protein kinase Cepsilon interacts with and inhibits the permeability transition pore in cardiac mitochondria". Circ. Res. 92 (8): 873–80. doi:10.1161/01.RES.0000069215.36389.8D. PMC 3691672. PMID 12663490.

[pmid23060438-21] Sun Y, Vashisht AA, Tchieu J, Wohlschlegel JA, Dreier L (Nov 2012). "Voltage-dependent anion channels (VDACs) recruit Parkin to defective mitochondria to promote mitochondrial autophagy". The Journal of Biological Chemistry 287 (48): 40652–60. doi:10.1074/jbc.M112.419721. PMID 23060438.

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VDAC1