The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

Links

 

Gene Review

OPA1  -  optic atrophy 1 (autosomal dominant)

Homo sapiens

Synonyms: Dynamin-like 120 kDa protein, mitochondrial, FLJ12460, KIAA0567, MGM1, NPG, ...
 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of OPA1

 

Psychiatry related information on OPA1

  • CONCLUSION: Attempted eyelid closure during tonometry is a significant and common source of error in eyes with glaucoma and may influence the clinical management and decision-making in the treatment of NTG and HTG [6].
 

High impact information on OPA1

 

Chemical compound and disease context of OPA1

  • METHODS: The forearm blood flow (FBF) was measured in 25 patients with essential hypertension and in 25 normotensive subjects by using strain-gauge plethysmography during reactive hyperemia (RH) (280 mm Hg for 5 min) and after sublingual administration of nitroglycerin (NTG, 0.3 mg) [11].
  • In NIDDM with HTG, chylomicrons appeared to be cleared at a slower rate, as evidenced by the significantly later intersection of the chylomicron and nonchylomicron retinyl palmitate response curves (13.7 h in HTG NIDDM vs. 8.5 h in NTG NIDDM vs. 7.3 h in controls; P less than 0.01) [12].
  • There was no significant difference between groups in the assessed parameters (95% CI for differences in Pao2/FIO2: furosemide/morphine -12 to 23 and NTG/NAC 4 to 44), a finding also confirmed in 32 patients presenting with respiratory failure [13].
  • Thus, the new NTG oral spray promises to afford therapeutic advantages for the relief of anginal attacks as well as hemodynamic unloading in congestive heart failure and acute pulmonary hypertension [14].
  • METHODS: 175 (250 eyes) POAG patients, 101 (190 eyes) glaucoma suspects with mild ocular hypertension, 39 (64 eyes) NTG patients and 163 (326 eyes) healthy volunteers underwent an ibopamine provocative test [15].
 

Biological context of OPA1

 

Anatomical context of OPA1

  • Dynamins are large GTPases that belong to a protein superfamily that, in eukaryotic cells, includes classical dynamins, dynamin-like proteins, OPA1, Mx proteins, mitofusins and guanylate-binding proteins/atlastins [19].
  • We successfully amplified OPA1 cDNA prepared from leukocyte RNA of three patients, and found the amount of transcripts harboring the Arg366Stop mutation was significantly reduced compared with transcripts derived from the normal chromosome [17].
  • Here we show that down-regulation of OPA1 in HeLa cells using specific small interfering RNA (siRNA) leads to fragmentation of the mitochondrial network concomitantly to the dissipation of the mitochondrial membrane potential and to a drastic disorganization of the cristae [20].
  • The strong association of OPA1 with membranes suggests its anchoring to the inner membrane [21].
  • The findings that OPA1-type DOA, as Leber optic neuropathy, is caused by the impairment of a mitochondrial protein address the question of the vulnerability of the retinal ganglion cell in response to mitochondrial defects [22].
 

Associations of OPA1 with chemical compounds

  • Subsequent sequencing of OPA1 identified a novel heterozygous missense mutation (c.1313A>G) replacing aspartic acid by glycine (p.D438G) in the GTPase domain of OPA1 [23].
  • Genetic analysis identified a G-->A substitution at nucleotide position 1334 in exon 14 of OPA1 causing an arginine-to-histidine change (R445H) in all affected members of the family [24].
  • METHODS: Japanese patients with normal tension glaucoma (NTG, n = 194), and high tension glaucoma (HTG, n = 191), and 185 control subjects were analyzed for the OPA1 intervening sequence (IVS) 8+4 cystosine thymine (C/T) and IVS 8+32 thymine cystosine (T/C) polymorphisms using pyrosequencing technique [25].
  • The whole plasma concentration of C apolipoproteins was essentially uninfluenced by the oral fat load, whereas the content in large triglyceride-rich lipoproteins paralleled the apo B elevations in controls and NTG patients [10].
  • We assigned 393 patients randomly to groups receiving acute cardiac catheterization and a double-blind intracoronary infusion of streptokinase (SK arm), both streptokinase and nitroglycerin (SK-NTG arm), nitroglycerin alone (NTG arm), or conventional therapy without acute catheterization (control arm) [26].
 

Other interactions of OPA1

  • Moreover, the recent identification of mutations in the nuclear gene OPA1 as the causative factor in dominant optic atrophy (DOA, Kjer's type) brought the unexpected finding that this gene encodes for a mitochondrial protein, suggesting that DOA and LHON may be linked by similar pathogenesis [27].
  • Its importance has been highlighted by the discovery that two human diseases are caused by mutations in the two mitochondrial pro-fusion genes, MFN2 and OPA1 [28].
  • Linkage analysis excluded OPA1 and OPA2 [29].
  • Similarly, in NIH-OVCAR-3 cells, the OPA1 siRNA induces mitochondrial fragmentation and apoptosis, the latter being inhibited by Bcl2 overexpression [20].
  • Evaluation included clinical examination, neuroimaging, and assessment of several mitochondrial parameters in the blood, including sequencing the entire mitochondrial (mt)DNA coding region, measuring relative mtDNA content, studying mitochondrial respiratory function in some patients, and sequencing the OPA1 and OPA3 genes [4].
 

Analytical, diagnostic and therapeutic context of OPA1

  • Loss of the intermembrane space protein Mgm1/OPA1 induces swelling and localized constrictions along the lengths of mitochondria [3].
  • Eighty-three well-characterized NTG patients were screened for mutations in OPA1 by heteroduplex analysis and bi-directional sequencing [30].
  • Proteolysis experiments indicate that OPA1 is present in the inter-membrane space and electron microscopy further localizes it close to the cristae [21].
  • Here we addressed the cell type-specific expression of the OPA1 protein in human brain sections using immunohistochemical techniques and Western blotting [31].
  • RESULTS: There were no differences in the OPA1 genotypes of the NTG and control groups at the +4 location, as had been suggested in a previous study, but a significant difference was observed at the +32 location of IVS8 [32].

References

  1. Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Delettre, C., Lenaers, G., Griffoin, J.M., Gigarel, N., Lorenzo, C., Belenguer, P., Pelloquin, L., Grosgeorge, J., Turc-Carel, C., Perret, E., Astarie-Dequeker, C., Lasquellec, L., Arnaud, B., Ducommun, B., Kaplan, J., Hamel, C.P. Nat. Genet. (2000) [Pubmed]
  2. OPA1 R445H mutation in optic atrophy associated with sensorineural deafness. Amati-Bonneau, P., Guichet, A., Olichon, A., Chevrollier, A., Viala, F., Miot, S., Ayuso, C., Odent, S., Arrouet, C., Verny, C., Calmels, M.N., Simard, G., Belenguer, P., Wang, J., Puel, J.L., Hamel, C., Malthièry, Y., Bonneau, D., Lenaers, G., Reynier, P. Ann. Neurol. (2005) [Pubmed]
  3. Loss of the intermembrane space protein Mgm1/OPA1 induces swelling and localized constrictions along the lengths of mitochondria. Griparic, L., van der Wel, N.N., Orozco, I.J., Peters, P.J., van der Bliek, A.M. J. Biol. Chem. (2004) [Pubmed]
  4. Mitochondrial Abnormalities in Patients with LHON-like Optic Neuropathies. Abu-Amero, K.K., Bosley, T.M. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  5. Investigating the association between OPA1 polymorphisms and glaucoma: comparison between normal tension and high tension primary open angle glaucoma. Aung, T., Ocaka, L., Ebenezer, N.D., Morris, A.G., Brice, G., Child, A.H., Hitchings, R.A., Lehmann, O.J., Bhattacharya, S.S. Hum. Genet. (2002) [Pubmed]
  6. Attempted eyelid closure affects intraocular pressure measurement in open-angle glaucoma patients. Jamal, K.N., Gürses-Ozden, R., Liebmann, J.M., Ritch, R. Am. J. Ophthalmol. (2002) [Pubmed]
  7. OPA1 and PARL keep a lid on apoptosis. Gottlieb, E. Cell (2006) [Pubmed]
  8. OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Alexander, C., Votruba, M., Pesch, U.E., Thiselton, D.L., Mayer, S., Moore, A., Rodriguez, M., Kellner, U., Leo-Kottler, B., Auburger, G., Bhattacharya, S.S., Wissinger, B. Nat. Genet. (2000) [Pubmed]
  9. Critical dependence of neurons on mitochondrial dynamics. Chen, H., Chan, D.C. Curr. Opin. Cell Biol. (2006) [Pubmed]
  10. Metabolism of triglyceride-rich lipoproteins during alimentary lipemia. Karpe, F., Steiner, G., Olivecrona, T., Carlson, L.A., Hamsten, A. J. Clin. Invest. (1993) [Pubmed]
  11. Effect of the angiotensin-converting enzyme inhibitor imidapril on reactive hyperemia in patients with essential hypertension: relationship between treatment periods and resistance artery endothelial function. Higashi, Y., Sasaki, S., Nakagawa, K., Matsuura, H., Kajiyama, G., Oshima, T. J. Am. Coll. Cardiol. (2001) [Pubmed]
  12. Fasting hypertriglyceridemia in noninsulin-dependent diabetes mellitus is an important predictor of postprandial lipid and lipoprotein abnormalities. Lewis, G.F., O'Meara, N.M., Soltys, P.A., Blackman, J.D., Iverius, P.H., Pugh, W.L., Getz, G.S., Polonsky, K.S. J. Clin. Endocrinol. Metab. (1991) [Pubmed]
  13. Nitrate therapy is an alternative to furosemide/morphine therapy in the management of acute cardiogenic pulmonary edema. Beltrame, J.F., Zeitz, C.J., Unger, S.A., Brennan, R.J., Hunt, A., Moran, J.L., Horowitz, J.D. J. Card. Fail. (1998) [Pubmed]
  14. Hemodynamic and coronary vasodilative action of two nitroglycerin oral spray formulations. Gansser, R.E., Schneeweiss, A., Weiss, M., Bachmann, K.F. Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy. (1990) [Pubmed]
  15. Ibopamine in glaucoma diagnostics: a new pharmacological provocative test. De Gregorio, F., Pecori Giraldi, J., Pannarale, L., Saccucci, S., Virno, M. International ophthalmology. (1996) [Pubmed]
  16. Spectrum, frequency and penetrance of OPA1 mutations in dominant optic atrophy. Toomes, C., Marchbank, N.J., Mackey, D.A., Craig, J.E., Newbury-Ecob, R.A., Bennett, C.P., Vize, C.J., Desai, S.P., Black, G.C., Patel, N., Teimory, M., Markham, A.F., Inglehearn, C.F., Churchill, A.J. Hum. Mol. Genet. (2001) [Pubmed]
  17. OPA1 mutations in patients with autosomal dominant optic atrophy and evidence for semi-dominant inheritance. Pesch, U.E., Leo-Kottler, B., Mayer, S., Jurklies, B., Kellner, U., Apfelstedt-Sylla, E., Zrenner, E., Alexander, C., Wissinger, B. Hum. Mol. Genet. (2001) [Pubmed]
  18. Deficit of in vivo mitochondrial ATP production in OPA1-related dominant optic atrophy. Lodi, R., Tonon, C., Valentino, M.L., Iotti, S., Clementi, V., Malucelli, E., Barboni, P., Longanesi, L., Schimpf, S., Wissinger, B., Baruzzi, A., Barbiroli, B., Carelli, V. Ann. Neurol. (2004) [Pubmed]
  19. The dynamin superfamily: universal membrane tubulation and fission molecules? Praefcke, G.J., McMahon, H.T. Nat. Rev. Mol. Cell Biol. (2004) [Pubmed]
  20. Loss of OPA1 perturbates the mitochondrial inner membrane structure and integrity, leading to cytochrome c release and apoptosis. Olichon, A., Baricault, L., Gas, N., Guillou, E., Valette, A., Belenguer, P., Lenaers, G. J. Biol. Chem. (2003) [Pubmed]
  21. The human dynamin-related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter-membrane space. Olichon, A., Emorine, L.J., Descoins, E., Pelloquin, L., Brichese, L., Gas, N., Guillou, E., Delettre, C., Valette, A., Hamel, C.P., Ducommun, B., Lenaers, G., Belenguer, P. FEBS Lett. (2002) [Pubmed]
  22. OPA1 (Kjer type) dominant optic atrophy: a novel mitochondrial disease. Delettre, C., Lenaers, G., Pelloquin, L., Belenguer, P., Hamel, C.P. Mol. Genet. Metab. (2002) [Pubmed]
  23. Structural model of the OPA1 GTPase domain may explain the molecular consequences of a novel mutation in a family with autosomal dominant optic atrophy. Dadgar, S., Hagens, O., Dadgar, S.R., Haghighi, E.N., Schimpf, S., Wissinger, B., Garshasbi, M. Exp. Eye Res. (2006) [Pubmed]
  24. Dominant optic atrophy, sensorineural hearing loss, ptosis, and ophthalmoplegia: a syndrome caused by a missense mutation in OPA1. Payne, M., Yang, Z., Katz, B.J., Warner, J.E., Weight, C.J., Zhao, Y., Pearson, E.D., Treft, R.L., Hillman, T., Kennedy, R.J., Meire, F.M., Zhang, K. Am. J. Ophthalmol. (2004) [Pubmed]
  25. The OPA1 Gene Polymorphism is Associated With Normal Tension and High Tension Glaucoma. Mabuchi, F., Tang, S., Kashiwagi, K., Yamagata, Z., Iijima, H., Tsukahara, S. Am. J. Ophthalmol. (2007) [Pubmed]
  26. Serial angiographic assessment of coronary artery obstruction and collateral flow in acute myocardial infarction. Report from the second Mount Sinai-New York University Reperfusion Trial. Rentrop, K.P., Feit, F., Sherman, W., Thornton, J.C. Circulation (1989) [Pubmed]
  27. Mitochondrial dysfunction as a cause of optic neuropathies. Carelli, V., Ross-Cisneros, F.N., Sadun, A.A. Progress in retinal and eye research. (2004) [Pubmed]
  28. Mitochondrial dynamics and disease, OPA1. Olichon, A., Guillou, E., Delettre, C., Landes, T., Arnauné-Pelloquin, L., Emorine, L.J., Mils, V., Daloyau, M., Hamel, C., Amati-Bonneau, P., Bonneau, D., Reynier, P., Lenaers, G., Belenguer, P. Biochim. Biophys. Acta (2006) [Pubmed]
  29. Progressive autosomal dominant optic atrophy and sensorineural hearing loss in a Turkish family. Ozden, S., Düzcan, F., Wollnik, B., Cetin, O.G., Sahiner, T., Bayramoğlu, I., Yüksel-Apak, M., Bağci, H. Ophthalmic Genet. (2002) [Pubmed]
  30. A major marker for normal tension glaucoma: association with polymorphisms in the OPA1 gene. Aung, T., Ocaka, L., Ebenezer, N.D., Morris, A.G., Krawczak, M., Thiselton, D.L., Alexander, C., Votruba, M., Brice, G., Child, A.H., Francis, P.J., Hitchings, R.A., Lehmann, O.J., Bhattacharya, S.S. Hum. Genet. (2002) [Pubmed]
  31. OPA1, associated with autosomal dominant optic atrophy, is widely expressed in the human brain. Bette, S., Schlaszus, H., Wissinger, B., Meyermann, R., Mittelbronn, M. Acta Neuropathol. (2005) [Pubmed]
  32. Polymorphisms in OPA1 are associated with normal tension glaucoma. Powell, B.L., Toomes, C., Scott, S., Yeung, A., Marchbank, N.J., Spry, P.G., Lumb, R., Inglehearn, C.F., Churchill, A.J. Mol. Vis. (2003) [Pubmed]
 
WikiGenes - Universities