Abstract
The gating of the Voltage-Dependent Anion Channel (VDAC) is linked to oxidative stress through increased generation of mitochondrial ROS with increasing mitochondrial membrane potential (ΔΨm). It has been already reported that H2O2 increases the single-channel conductance of VDAC on a bilayer lipid membrane. On the other hand, homocysteine (Hcy) has been reported to induce mitochondria-mediated cell death. It is argued that the thiol-form of homocysteine, HTL could be the plausible molecule responsible for the alteration in the function of proteins, such as VDAC. It is hypothesized that HTL interacts with VDAC that causes functional abnormalities. An investigation was undertaken to study the interaction of HTL with VDAC under H2O2 induced oxidative stress through biophysical and electrophysiological methods. Fluorescence spectroscopic studies indicate that HTL interacts with VDAC, but under induced oxidative stress the effect is prevented partially. Similarly, bilayer electrophysiology studies suggest that HTL shows a reduction in VDAC single-channel conductance, but the effects are partially prevented under an oxidative environment. Gly172 and His181 are predicted through bioinformatics tools to be the most plausible binding residues of HTL in Rat VDAC. The binding of HTL and H2O2 with VDAC appears to be cooperative as per our analysis of experimental data in the light of the Hill-Langmuir equation. The binding energies are estimated to be − 4.7 kcal mol−1 and − 2.8 kcal mol−1, respectively. The present in vitro studies suggest that when mitochondrial VDAC is under oxidative stress, the effects of amino acid metabolites like HTL are suppressed.
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References
Álvarez-Maqueda M, El Bekay R, Monteseirín J et al (2004) Homocysteine enhances superoxide anion release and NADPH oxidase assembly by human neutrophils: effects on MAPK activation and neutrophil migration. Atherosclerosis 172:229–238. https://doi.org/10.1016/j.atherosclerosis.2003.11.005
Attie AD, Raines RT (1995) Analysis of receptor-ligand interactions. J Chem Educ 72:119–124. https://doi.org/10.1021/ed072p119
Austin RC, Sood SK, Dorward AM et al (1998) Homocysteine-dependent alterations in mitochondrial gene expression, function and structure: homocysteine and H2O2 act synergistically to enhance mitochondrial damage. J Biol Chem 273:30808–30817. https://doi.org/10.1074/jbc.273.46.30808
Avdonin PV, Nadeev AD, Mironova GY et al (2019) Enhancement by hydrogen peroxide of calcium signals in endothelial cells induced by 5-HT1B and 5-HT2B receptor agonists. Oxid Med Cell Longev. https://doi.org/10.1155/2019/1701478
Aykin-Burns N, Ahmad IM, Zhu Y et al (2009) Increased levels of superoxide and H2O2 mediate the differential susceptibility of cancer cells versus normal cells to glucose deprivation. Biochem J 418:29–37. https://doi.org/10.1042/BJ20081258
Azoulay-Zohar H, Israelson A, Abu-Hamad S, Shoshan-Barmatz V (2004) In self-defence: hexokinase promotes voltage-dependent anion channel closure and prevents mitochondria-mediated apoptotic cell death. Biochem J 377:347–355. https://doi.org/10.1042/BJ20031465
Banerjee J, Ghosh S (2006) Phosphorylation of rat brain mitochondrial voltage-dependent anion as a potential tool to control leakage of cytochrome c. J Neurochem 98:670–676. https://doi.org/10.1111/j.1471-4159.2006.03853.x
Banerjee J, Ghosh S (2004) Interaction of mitochondrial voltage-dependent anion channel from rat brain with plasminogen protein leads to partial closure of the channel. Biochim Biophys Acta - Biomembr 1663:6–8. https://doi.org/10.1016/j.bbamem.2004.02.005
Báthori G, Csordás G, Garcia-Perez C et al (2006) Ca2+-dependent control of the permeability properties of the mitochondrial outer membrane and voltage-dependent anion-selective channel (VDAC). J Biol Chem 281:17347–17358. https://doi.org/10.1074/jbc.M600906200
Bayrhuber M, Meins T, Habeck M et al (2008) Structure of the human voltage-dependent anion channel. Proc Natl Acad Sci USA 105:15370–15375. https://doi.org/10.1073/pnas.0808115105
Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87:245–313
Bejarano I, Espino J, González-Flores D et al (2009) Role of calcium signals on hydrogen peroxide-induced apoptosis in human myeloid HL-60 cells. Int J Biomed Sci 5:246–256
Ben-Hail D, Shoshan-Barmatz V (2014) Purification of VDAC1 from rat liver mitochondria. Cold Spring Harb Protoc 2014:94–99. https://doi.org/10.1101/pdb.prot073130
Bera AK, Ghosh S (2001) Dual mode of gating of voltage-dependent anion channel as revealed by phosphorylation. J Struct Biol 135:67–72. https://doi.org/10.1006/jsbi.2001.4399
Bharathselvi M, Biswas J, Selvi R et al (2013) Increased homocysteine, homocysteine-thiolactone, protein homocysteinylation and oxidative stress in the circulation of patients with Eales’ disease. Ann Clin Biochem 50:330–338. https://doi.org/10.1177/0004563213492146
Brand MD (2016) Mitochondrial generation of superoxide and hydrogen peroxide as the source of mitochondrial redox signaling. Free Radic Biol Med 100:14–31
Cankurtaran M, Yesil Y, Kuyumcu ME et al (2013) Altered levels of homocysteine and serum natural antioxidants links oxidative damage to Alzheimer’s disease. J Alzheimer’s Dis 33:1051–1058. https://doi.org/10.3233/JAD-2012-121630
Castro J, Bittner CX, Humeres A et al (2004) A cytosolic source of calcium unveiled by hydrogen peroxide with relevance for epithelial cell death. Cell Death Differ 11:468–478
Checchetto V, Reina S, Magrì A et al (2014) Recombinant human voltage dependent anion selective channel isoform 3 (hVDAC3) forms pores with a very small conductance. Cell Physiol Biochem 34:842–853. https://doi.org/10.1159/000363047
Chen WT, Kuo YY, Lin GB et al (2020) Thermal cycling protects SH-SY5Y cells against hydrogen peroxide and β-amyloid-induced cell injury through stress response mechanisms involving Akt pathway. PLoS ONE. https://doi.org/10.1371/journal.pone.0240022
Chwatko G, Boers GHJ, Strauss KA et al (2007) Mutations in methylenetetrahydrofolate reductase or cystathionine β-syntase gene, or a high-methionine diet, increase homocysteine thiolactone levels in humans and mice. FASEB J 21:1707–1713. https://doi.org/10.1096/fj.06-7435com
Clarke R, Smith AD, Jobst KA et al (1998) Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 55:1449–1455. https://doi.org/10.1001/archneur.55.11.1449
Colombini M (1979) A candidate for the permeability pathway of the outer mitochondrial membrane [19]. Nature 279:643–645
de Pinto V, Prezioso G, Palmieri F (1987) A simple and rapid method for the purification of the mitochondrial porin from mammalian tissues. BBA Biomembr 905:499–502. https://doi.org/10.1016/0005-2736(87)90480-9
De Pinto V, Reina S, Guarino F, Messina A (2008) Structure of the voltage dependent anion channel: state of the art. J Bioenerg Biomembr 40:139–147. https://doi.org/10.1007/s10863-008-9140-3
De Stefani D, Bononi A, Romagnoli A et al (2012) VDAC1 selectively transfers apoptotic Ca 2 signals to mitochondria. Cell Death Differ 19:267–273. https://doi.org/10.1038/cdd.2011.92
DeHart DN, Fang D, Heslop K et al (2018) Opening of voltage dependent anion channels promotes reactive oxygen species generation, mitochondrial dysfunction and cell death in cancer cells. Biochem Pharmacol 148:155–162. https://doi.org/10.1016/j.bcp.2017.12.022
Del Río LA, López-Huertas E (2016) ROS generation in peroxisomes and its role in cell signaling. Plant Cell Physiol 57:1364–1376
Dröge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95
Dubey AK, Godbole A, Mathew MK (2016) Regulation of VDAC trafficking modulates cell death. Cell Death Discov. https://doi.org/10.1038/cddiscovery.2016.85
Eskes R, Desagher S, Antonsson B, Martinou J-C (2000) Bid Induces the oligomerization and insertion of bax into the outer mitochondrial membrane. Mol Cell Biol 20:929–935. https://doi.org/10.1128/mcb.20.3.929-935.2000
Fiek C, Benz R, Roos N, Brdiczka D (1982) Evidence for identity between the hexokinase-binding protein and the mitochondrial porin in the outer membrane of rat liver mitochondria. BBA - Biomembr 688:429–440. https://doi.org/10.1016/0005-2736(82)90354-6
Forman HJ, Bernardo A, Davies KJA (2016) What is the concentration of hydrogen peroxide in blood and plasma? Arch Biochem Biophys 603:48–53
Gandhi S, Abramov AY (2012) Mechanism of oxidative stress in neurodegeneration. Oxid. Med. Cell. Longev.
Gesztelyi R, Zsuga J, Kemeny-Beke A et al (2012) The Hill equation and the origin of quantitative pharmacology. Arch Hist Exact Sci 66:427–438
Gincel D, Shoshan-Barmatz V (2004) Glutamate interacts with VDAC and modulates opening of the mitochondrial permeability transition pore. J Bioenerg Biomembr 36:179–186. https://doi.org/10.1023/B:JOBB.0000023621.72873.9e
Gincel D, Zaid H, SHOSHAN-BARMATZ V, (2001) Calcium binding and translocation by the voltage-dependent anion channel: a possible regulatory mechanism in mitochondrial function. Biochem J 358:147–155. https://doi.org/10.1042/bj3580147
Gonz A, Granados P, Pariente A (2005) H2O2-induced changes in mitochondrial activity in isolated mouse pancreatic acinar cells. Mol Cell Biochem 269:165–173
Gupta R, Ghosh S (2017a) JNK3 phosphorylates Bax protein and induces ability to form pore on bilayer lipid membrane. Biochim Open 4:41–46. https://doi.org/10.1016/j.biopen.2017.02.001
Gupta R, Ghosh S (2017b) Phosphorylation of purified mitochondrial Voltage-Dependent Anion Channel by c-Jun N-terminal Kinase-3 modifies channel voltage-dependence. Biochim Open 4:78–87. https://doi.org/10.1016/j.biopen.2017.03.002
Gupta R, Ghosh S (2015) Phosphorylation of voltage-dependent anion channel by c-Jun N-terminal Kinase-3 leads to closure of the channel. Biochem Biophys Res Commun 459:100–106. https://doi.org/10.1016/j.bbrc.2015.02.077
Gurda D, Handschuh L, Kotkowiak W, Jakubowski H (2015) Homocysteine thiolactone and N-homocysteinylated protein induce pro-atherogenic changes in gene expression in human vascular endothelial cells. Amino Acids 47:1319–1339. https://doi.org/10.1007/s00726-015-1956-7
Heslop KA, Rovini A, Hunt EG et al (2020) JNK activation and translocation to mitochondria mediates mitochondrial dysfunction and cell death induced by VDAC opening and sorafenib in hepatocarcinoma cells. Biochem Pharmacol. https://doi.org/10.1016/j.bcp.2019.113728
Hodge T, Colombini M (1997) Regulation of metabolite flux through voltage-gating of VDAC channels. J Membr Biol 157:271–279. https://doi.org/10.1007/s002329900235
Holmström KM, Finkel T (2014) Cellular mechanisms and physiological consequences of redox-dependent signalling. Nat Rev Mol Cell Biol 15:411–421
Hu Q, Corda S, Zweier JL et al (1998) Hydrogen peroxide induces intracellular calcium oscillations in human aortic endothelial cells. Circulation 97:268–275. https://doi.org/10.1161/01.CIR.97.3.268
Hu T, Chen K, Hu L et al (2016) H2O2 and Ca2+-based signaling and associated ion accumulation, antioxidant systems and secondary metabolism orchestrate the response to NaCl stress in perennial ryegrass. Sci Rep. https://doi.org/10.1038/srep36396
Huang RFS, Huang SM, Lin BS et al (2001) Homocysteine thiolactone induces apoptotic DNA damage mediated by increased intracellular hydrogen peroxide and caspase 3 activation in HL-60 cells. Life Sci 68:2799–2811. https://doi.org/10.1016/S0024-3205(01)01066-9
Jakubowski H (1997) Metabolism of homocysteine thiolactone in human cell cultures: possible mechanism for pathological consequences of elevated homocysteine levels. J Biol Chem 272:1935–1942
Jakubowski H (2019) Homocysteine modification in protein structure/function and human disease. Physiol Rev 99:555–604. https://doi.org/10.1152/physrev.00003.2018
Jakubowski H (2002) The determination of homocysteine-thiolactone in biological samples. Anal Biochem 308:112–119. https://doi.org/10.1016/S0003-2697(02)00224-5
Jakubowski H, Boers GHJ, Strauss KA (2008) Mutations in cystathionine β-synthase or methylenetetrahydrofolate reductase gene increase N -homocysteinylated protein levels in humans. FASEB J 22:4071–4076. https://doi.org/10.1096/fj.08-112086
Kardaras F, Kardara DF (1995) Hyperhomocysteinemia An Independent Risk Factor for Vascular Disease _ Enhanced Reader. Hell J Cardiol 36:275–279
Keinan N, Pahima H, Ben-Hail D, Shoshan-Barmatz V (2013) The role of calcium in VDAC1 oligomerization and mitochondria-mediated apoptosis. Biochim Biophys Acta Mol Cell Res 1833:1745–1754. https://doi.org/10.1016/j.bbamcr.2013.03.017
Keinan N, Tyomkin D, Shoshan-Barmatz V (2010) Oligomerization of the mitochondrial protein voltage-dependent anion channel is coupled to the induction of apoptosis. Mol Cell Biol 30:5698–5709. https://doi.org/10.1128/mcb.00165-10
Kl T, N Q, T S, et al (2005) High homocysteine and low B vitamins predict cognitive decline in. Veterans Aff Norm Aging Study Am J Clin Nutr 82:627–635
Korshunov SS, Skulachev VP, Starkov AA (1997) High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett 416:15–18. https://doi.org/10.1016/S0014-5793(97)01159-9
Krammer EM, Vu GT, Homblé F, Prévost M (2015) Dual mechanism of ion permeation through VDAC revealed with inorganic phosphate ions and phosphate metabolites. PLoS ONE. https://doi.org/10.1371/journal.pone.0121746
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685. https://doi.org/10.1038/227680a0
Laskowski RA, Swindells MB (2011) LigPlot+: Multiple ligand-protein interaction diagrams for drug discovery. J Chem Inf Model 51:2778–2786. https://doi.org/10.1021/ci200227u
Lassègue B, San Martín A, Griendling KK (2012) Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system. Circ Res 110:1364–1390
Lee AC, Xu X, Blachly-Dyson E et al (1998a) The role of yeast VDAC genes on the permeability of the mitochondrial outer membrane. J Membr Biol 161:173–181. https://doi.org/10.1007/s002329900324
Lee S, Tak E, Lee J et al (2011) Mitochondrial H2O2 generated from electron transport chain complex i stimulates muscle differentiation. Cell Res 21:817–834. https://doi.org/10.1038/cr.2011.55
Lee SR, Kwont KS, Kim SR, Rhee SG (1998b) Reversible inactivation of protein-tyrosine phosphatase 1B in A431 cells stimulated with epidermal growth factor. J Biol Chem 273:15366–15372. https://doi.org/10.1074/jbc.273.25.15366
Lehmann M, Gottfries CG, Regland B (1999) Identification of cognitive impairment in the elderly: Homocysteine is an early marker. Dement Geriatr Cogn Disord 10:12–20. https://doi.org/10.1159/000017092
Lemasters JJ (2017) Evolution of voltage-dependent anion channel function: From molecular sieve to governator to actuator of ferroptosis. Front Oncol. https://doi.org/10.3389/fonc.2017.00303
Li Q, Duan MJ, Li SS et al (2016) Recognition and binding of voltage-dependent anion channel-1 with ATP and NADH by spectroscopic analysis and molecular docking. RSC Adv 6:13407–13417. https://doi.org/10.1039/c5ra27694b
Liou G-Y, Storz P (2010) Reactive oxygen species in cancer. Free Radic Res 44:479–496. https://doi.org/10.3109/10715761003667554
Lipper CH, Stofleth JT, Bai F et al (2019) Redox-dependent gating of VDAC by mitoNEET. Proc Natl Acad Sci USA 116:19924–19929. https://doi.org/10.1073/pnas.1908271116
Liu HH, Shih TS, Huang HR et al (2013) Plasma homocysteine is associated with increased oxidative stress and antioxidant enzyme activity in welders. Sci World J. https://doi.org/10.1155/2013/370487
Liu N, Li Y, Nan W et al (2020) Interaction of TPPP3 with VDAC1 promotes endothelial injury through activation of reactive oxygen species. Oxid Med Cell Longev. https://doi.org/10.1155/2020/5950195
Lominadze D, Roberts AM, Tyagi N et al (2006) Homocysteine causes cerebrovascular leakage in mice. Am J Physiol - Hear Circ Physiol 290:1206–1213. https://doi.org/10.1152/ajpheart.00376.2005
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275. https://doi.org/10.1016/s0021-9258(19)52451-6
Lu L, Zhang C, Cai Q et al (2013) Voltage-dependent anion channel involved in the -synuclein-induced dopaminergic neuron toxicity in rats. Acta Biochim Biophys Sin (shanghai) 45:170–178. https://doi.org/10.1093/abbs/gms114
Ludwig O, De Pinto V, Palmieri F, Benz R (1986) Pore formation by the mitochondrial porin of rat brain in lipid bilayer membranes. BBA - Biomembr 860:268–276. https://doi.org/10.1016/0005-2736(86)90523-7
Madesh M, Hajnóczky G (2001) VDAC-dependent permeabilization of the outer mitochondrial membrane by superoxide induces rapid and massive cytochrome c release. J Cell Biol 155:1003–1015. https://doi.org/10.1083/jcb.200105057
Mailloux RJ (2015) Teaching the fundamentals of electron transfer reactions in mitochondria and the production and detection of reactive oxygen species. Redox Biol 4:381–398
Majewski N, Nogueira V, Bhaskar P et al (2004) Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak. Mol Cell 16:819–830. https://doi.org/10.1016/j.molcel.2004.11.014
Maldonado EN (2017) VDAC-tubulin, an anti-Warburg pro-oxidant switch. Front. Oncol. 7
Malik C, Ghosh S (2020a) Regulation of single-channel conductance of voltage-dependent anion channel by mercuric chloride in a planar lipid bilayer. J Membr Biol 253:357–371. https://doi.org/10.1007/s00232-020-00134-1
Malik C, Ghosh S (2020b) Modulation of the mitochondrial voltage-dependent anion channel (VDAC) by hydrogen peroxide and its recovery by curcumin. Eur Biophys J 49:661–672. https://doi.org/10.1007/s00249-020-01469-2
Malik C, Ghosh S (2020) Quinidine partially blocks mitochondrial voltage-dependent anion channel (VDAC). Eur Biophys J 49:193–205. https://doi.org/10.1007/s00249-020-01426-z
Malik C, Siddiqui SI, Ghosh S (2021) Extracellular Signal-Regulated Kinase1 (ERK1)-Mediated Phosphorylation of Voltage-Dependent Anion Channel (VDAC) Suppresses its Conductance. J Membr Biol. https://doi.org/10.1007/s00232-021-00205-x
Markwell MAK, Haas SM, Tolbert NE, Bieber LL (1981) Protein determination in membrane and lipoprotein samples: manual and automated procedures. Methods in Enzymology. Academic Press, London, pp 296–303
McCaddon A, Davies G, Hudson P et al (1998) Total serum homocysteine in senile dementia of Alzheimer type. Int J Geriatr Psychiatry 13:235–239. https://doi.org/10.1002/(SICI)1099-1166(199804)13:4%3c235::AID-GPS761%3e3.0.CO;2-8
Menzel VA, Cassará MC, Benz R et al (2009) Molecular and functional characterization of VDAC2 purified from mammal spermatozoa. Biosci Rep 29:351–362. https://doi.org/10.1042/BSR20080123
Mercié P, Garnier O, Lascoste L et al (2000) Homocysteine-thiolactone induces caspase-independent vascular endothelial cell death with apoptotic features. Apoptosis 5:403–411. https://doi.org/10.1023/A:1009652011466
Messina A, Reina S, Guarino F, De Pinto V (2012) VDAC isoforms in mammals. Biochim Biophys Acta - Biomembr 1818:1466–1476. https://doi.org/10.1016/j.bbamem.2011.10.005
Milton NGN (2008) Homocysteine inhibits hydrogen peroxide breakdown by catalase. Open Enzym Inhib J 1:34–41. https://doi.org/10.2174/1874940200801010034
Morris GM, Ruth H, Lindstrom W et al (2009) Software news and updates AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 30:2785–2791. https://doi.org/10.1002/jcc.21256
Motulsky HJ, Neubig RR (2010) Analyzing binding data. Curr Protoc Neurosci. https://doi.org/10.1002/0471142301.ns0705s52
Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13
Nulton-Persson AC, Szweda LI (2001) Modulation of mitochondrial function by hydrogen peroxide. J Biol Chem 276:23357–23361. https://doi.org/10.1074/jbc.M100320200
Park E, Lee GJ, Choi S et al (2010) The role of glutamate release on voltage-dependent anion channels (VDAC)-mediated apoptosis in an eleven vessel occlusion model in rats. PLoS ONE. https://doi.org/10.1371/journal.pone.0015192
Pervin S, Singh R, Rosenfeld ME et al (1998) Estradiol suppresses MCP-1 expression in vivo: Implications for atherosclerosis. Arterioscler Thromb Vasc Biol 18:1575–1582. https://doi.org/10.1161/01.ATV.18.10.1575
Peskin AV, Pace PE, Behring JB et al (2016) Glutathionylation of the active site cysteines of peroxiredoxin 2 and recycling by glutaredoxin. J Biol Chem 291:3053–3062. https://doi.org/10.1074/jbc.M115.692798
Queralt-Martín M, Bergdoll L, Teijido O et al (2020) A lower affinity to cytosolic proteins reveals VDAC3 isoform-specific role in mitochondrial biology. J Gen Physiol. https://doi.org/10.1085/JGP.201912501
Raghavan A, Sheiko T, Graham BH, Craigen WJ (2012) Voltage-dependant anion channels: Novel insights into isoform function through genetic models. Biochim Biophys Acta - Biomembr 1818:1477–1485. https://doi.org/10.1016/j.bbamem.2011.10.019
Rašić-Marković A, Stanojlović O, Hrnčić D et al (2009) The activity of erythrocyte and brain Na+/K+ and Mg2+-ATPases in rats subjected to acute homocysteine and homocysteine thiolactone administration. Mol Cell Biochem 327:39–45. https://doi.org/10.1007/s11010-009-0040-6
Reina S, Palermo V, Guarnera A et al (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 Lett 584:2837–2844. https://doi.org/10.1016/j.febslet.2010.04.066
Reina S, Pittalà MGG, Guarino F et al (2020) Cysteine Oxidations in Mitochondrial Membrane Proteins: The Case of VDAC Isoforms in Mammals. Front Cell Dev Biol 8:1–15. https://doi.org/10.3389/fcell.2020.00397
Roos N, Benz R, Brdiczka D (1982) Identification and characterization of the pore-forming protein in the outer membrane of rat liver mitochondria
Rosenquist TH, Ratashak SA, Selhub J (1996) Homocysteine induces congenital defects of the heart and neural tube: Effect of folic acid. Proc Natl Acad Sci USA 93:15227–15232. https://doi.org/10.1073/pnas.93.26.15227
Rostovtseva T, Colombini M (1997) Vdac channels mediate and gate the flow of ATP: implications for the regulation of mitochondrial function. Biophys J 72:1954–1962. https://doi.org/10.1016/S0006-3495(97)78841-6
Roybal CN, Yang S, Sun CW et al (2004) Homocysteine increases the expression of vascular endothelial growth factor by a mechanism involving endoplasmic reticulum stress and transcription factor ATF4. J Biol Chem 279:14844–14852. https://doi.org/10.1074/jbc.M312948200
Saletti R, Reina S, Pittalà MGG et al (2018) Post-translational modifications of VDAC1 and VDAC2 cysteines from rat liver mitochondria. Biochim Biophys Acta - Bioenergy 1859:806–816. https://doi.org/10.1016/j.bbabio.2018.06.007
Schein SJ, Colombini M, Finkelstein A (1976) Reconstitution in planar lipid bilayers of a voltage-dependent anion-selective channel obtained from paramecium mitochondria. J Membr Biol 30:99–120. https://doi.org/10.1007/BF01869662
Sen U, Basu P, Abe OA et al (2009) Hydrogen sulfide ameliorates hyperhomocysteinemia-associated chronic renal failure. Am J Physiol - Ren Physiol 297:410–419. https://doi.org/10.1152/ajprenal.00145.2009
Shoshan-Barmatz V, De S, Meir A (2017) The mitochondrial voltage-dependent anion channel 1, Ca2+ transport, apoptosis, and their regulation. Front Oncol. https://doi.org/10.3389/fonc.2017.00060
Shrivastava R, Ghosh S (2021) Collective dynamics of ion channels on bilayer lipid membranes. ACS Omega 6:7544–7557. https://doi.org/10.1021/acsomega.°C06061
Sies H (2017) Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: oxidative eustress. Redox Biol 11:613–619
Sindrewicz P, Li X, Yates EA et al (2019) Intrinsic tryptophan fluorescence spectroscopy reliably determines galectin-ligand interactions. Sci Rep. https://doi.org/10.1038/s41598-019-47658-8
Srejovic I, Jakovljevic V, Zivkovic V et al (2015) The effects of the modulation of NMDA receptors by homocysteine thiolactone and dizocilpine on cardiodynamics and oxidative stress in isolated rat heart. Mol Cell Biochem 401:97–105. https://doi.org/10.1007/s11010-014-2296-8
Sun L, Shukair S, Naik TJ et al (2008) Glucose phosphorylation and mitochondrial binding are required for the protective effects of hexokinases I and II. Mol Cell Biol 28:1007–1017. https://doi.org/10.1128/mcb.00224-07
Tan W, Colombini M (2007) VDAC closure increases calcium ion flux. Biochim Biophys Acta - Biomembr 1768:2510–2515. https://doi.org/10.1016/j.bbamem.2007.06.002
Trott O, Olson AJ (2009) AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem NA-NA. https://doi.org/10.1002/jcc.21334
Tsai MY, Hanson NQ, Bignell MK, Schwichtenberg KA (1996) Simultaneous detection and screening of T833C and G919A mutations of the cystathionine β-synthase gene by single-strand conformational polymorphism. Clin Biochem 29:473–477. https://doi.org/10.1016/0009-9120(96)00045-8
Ujwal R, Cascio D, Colletier JP et al (2008) The crystal structure of mouse VDAC1 at 2.3 Å resolution reveals mechanistic insights into metabolite gating. Proc Natl Acad Sci USA 105:17742–17747. https://doi.org/10.1073/pnas.0809634105
Villinger S, Giller K, Bayrhuber M et al (2014) Nucleotide interactions of the human voltage-dependent anion channel. J Biol Chem 289:13397–13406. https://doi.org/10.1074/jbc.M113.524173
Wang L, Jhee KH, Hua X et al (2004) Modulation of cystathionine β-synthase level regulates total serum homocysteine in mice. Circ Res 94:1318–1324. https://doi.org/10.1161/01.RES.0000129182.46440.4a
Xu X, Decker W, Sampson MJ et al (1999) Mouse VDAC isoforms expressed in yeast: channel properties and their roles in mitochondrial outer membrane permeability. J Membr Biol 170:89–102. https://doi.org/10.1007/s002329900540
Yamamoto T, Yamada A, Watanabe M et al (2006) 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. J Proteome Res 5:3336–3344. https://doi.org/10.1021/pr060291w
Yehezkel G, Hadad N, Zaid H et al (2006) Nucleotide-binding sites in the voltage-dependent anion channel: characterization and localization. J Biol Chem 281:5938–5946. https://doi.org/10.1074/jbc.M510104200
Zhuo J-M, Portugal SG, Kruger DW et al (2010) Diet-induced hyperhomocysteinemia increases amyloid-β formation and deposition in a mouse model of Alzheimers disease. Curr Alzheimer Res 7:140–149
Zivkovic V, Jakovljevic V, Pechanova O et al (2013) Effects of DL-homocysteine thiolactone on cardiac contractility, coronary flow, and oxidative stress markers in the isolated rat heart: The role of different gasotransmitters. Biomed Res Int. https://doi.org/10.1155/2013/318471
Zizi M, Forte M, Blachly-Dyson E, Colombini M (1994) NADH regulates the gating of VDAC, the mitochondrial outer membrane channel. J Biol Chem 269:1614–1616. https://doi.org/10.1016/s0021-9258(17)42070-9
Acknowledgements
T Daniel Tuikhang Koren thanks the University Grants Commission (UGC), New Delhi, India, for providing the Senior Research Fellowship. Both the authors extend their thanks to Jitender Kumar and Rajan Shrivastava for scripting the Python scripts as well as for their valuable suggestions and other technical assists. This work was supported by the Department of Biophysics, University of Delhi South Campus, New Delhi-110021, India.
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Both the authors contributed to the concept, design, and analysis of the work. Materials preparations and data acquisition were performed by T Daniel Tuikhang Koren. Both the authors jointly wrote the manuscript.
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All animal experiments were performed as per norms of the Institutional Animal Ethics Committee (IAEC) under the supervision of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), India (Lic. No.: 48/1AEC/SG/Biophy/UDSC/07.09.2019).
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Koren, T.D.T., Ghosh, S. Homocysteine-Thiolactone Modulates Gating of Mitochondrial Voltage-Dependent Anion Channel (VDAC) and Protects It from Induced Oxidative Stress. J Membrane Biol 255, 79–97 (2022). https://doi.org/10.1007/s00232-022-00215-3
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DOI: https://doi.org/10.1007/s00232-022-00215-3