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Gene Review

DNM1L  -  dynamin 1-like

Homo sapiens

Synonyms: DLP1, DRP1, DVLP, DYMPLE, Dnm1p/Vps1p-like protein, ...
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Disease relevance of DNM1L


High impact information on DNM1L


Biological context of DNM1L


Anatomical context of DNM1L


Associations of DNM1L with chemical compounds

  • When the full-length cDNA of HdynIV was sequenced, it showed that HdynIV's carboxyl terminal lacks a proline-rich domain that can bind to Gsk-3 beta [16].
  • Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons [17].
  • Consequently, in Drp-1-expressing cells the apoptotic efficacy of ceramide, which causes a Ca2+-dependent perturbation of mitochondrial structure and function, was drastically reduced [18].
  • DRP-1/Ku DNA binding was assessed in mobility shift assays and competition binding assays using cisplatin-damaged DNA [19].
  • This could be a dynamin-like GTP-ase, since GTP gamma S-stimulated tubule formation has only been reported previously in cases where a dynamin is involved [20].
  • We have identified cAMP-dependent protein kinase-dependent phosphorylation of Drp1 within the GED domain at Ser(637) that inhibits Drp1 GTPase activity [21].
  • Drp1 phosphorylation at Ser 656 provides a mechanism for the integration of cAMP and calcium signals in the control of mitochondrial shape, apoptosis and other aspects of mitochondrial function [22].

Physical interactions of DNM1L


Other interactions of DNM1L

  • The yeast protein Fis1p has been shown to participate in mitochondrial fission mediated by the dynamin-related protein Dnm1p [24].
  • We have screened about 16,000 small molecules and have identified 1, named here dynasore, that interferes in vitro with the GTPase activity of dynamin1, dynamin2, and Drp1, the mitochondrial dynamin, but not of other small GTPases [25].
  • Co-transfection of DLP1 siRNA with Pex11pbeta, a peroxisomal membrane protein involved in peroxisome proliferation, induced further elongation and network formation of the peroxisomal compartment [26].
  • Together, these findings indicate that yeast and mammalian cells have a conserved programmed death pathway regulated by a common molecular component, Drp1/Dnm1, that is inhibited by a Bcl-2-like function [27].
  • Misregulated interaction between DLP1 and hFis1 by alpha1 deletion induced mitochondrial swelling, in part by the mitochondrial permeability transition, but significantly delayed cell death [28].

Analytical, diagnostic and therapeutic context of DNM1L


  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. Mitochondrial fission in apoptosis, neurodegeneration and aging. Bossy-Wetzel, E., Barsoum, M.J., Godzik, A., Schwarzenbacher, R., Lipton, S.A. Curr. Opin. Cell Biol. (2003) [Pubmed]
  3. Mutation spectrum and splicing variants in the OPA1 gene. Delettre, C., Griffoin, J.M., Kaplan, J., Dollfus, H., Lorenz, B., Faivre, L., Lenaers, G., Belenguer, P., Hamel, C.P. Hum. Genet. (2001) [Pubmed]
  4. Genomic organization, alternative splicing, and promoter analysis of human dynamin-like protein gene. Howng, S.L., Sy, W.D., Cheng, T.S., Lieu, A.S., Wang, C., Tzou, W.S., Cho, C.L., Hong, Y.R. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  5. OPA1 and PARL keep a lid on apoptosis. Gottlieb, E. Cell (2006) [Pubmed]
  6. Mitochondrial Inner-Membrane Fusion and Crista Maintenance Requires the Dynamin-Related GTPase Mgm1. Meeusen, S., Devay, R., Block, J., Cassidy-Stone, A., Wayson, S., McCaffery, J.M., Nunnari, J. Cell (2006) [Pubmed]
  7. 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]
  8. Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis. Lee, Y.J., Jeong, S.Y., Karbowski, M., Smith, C.L., Youle, R.J. Mol. Biol. Cell (2004) [Pubmed]
  9. Normal mitochondrial dynamics requires rhomboid-7 and affects Drosophila lifespan and neuronal function. McQuibban, G.A., Lee, J.R., Zheng, L., Juusola, M., Freeman, M. Curr. Biol. (2006) [Pubmed]
  10. Subplasmalemmal mitochondria modulate the activity of plasma membrane Ca2+-ATPases. Frieden, M., Arnaudeau, S., Castelbou, C., Demaurex, N. J. Biol. Chem. (2005) [Pubmed]
  11. Dymple, a novel dynamin-like high molecular weight GTPase lacking a proline-rich carboxyl-terminal domain in mammalian cells. Kamimoto, T., Nagai, Y., Onogi, H., Muro, Y., Wakabayashi, T., Hagiwara, M. J. Biol. Chem. (1998) [Pubmed]
  12. Caspase cleavage product of BAP31 induces mitochondrial fission through endoplasmic reticulum calcium signals, enhancing cytochrome c release to the cytosol. Breckenridge, D.G., Stojanovic, M., Marcellus, R.C., Shore, G.C. J. Cell Biol. (2003) [Pubmed]
  13. The dynamin superfamily: universal membrane tubulation and fission molecules? Praefcke, G.J., McMahon, H.T. Nat. Rev. Mol. Cell Biol. (2004) [Pubmed]
  14. A human dynamin-related protein controls the distribution of mitochondria. Smirnova, E., Shurland, D.L., Ryazantsev, S.N., van der Bliek, A.M. J. Cell Biol. (1998) [Pubmed]
  15. Endoplasmic reticulum BIK initiates DRP1-regulated remodelling of mitochondrial cristae during apoptosis. Germain, M., Mathai, J.P., McBride, H.M., Shore, G.C. EMBO J. (2005) [Pubmed]
  16. Human dynamin-like protein interacts with the glycogen synthase kinase 3beta. Hong, Y.R., Chen, C.H., Cheng, D.S., Howng, S.L., Chow, C.C. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  17. Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons. Barsoum, M.J., Yuan, H., Gerencser, A.A., Liot, G., Kushnareva, Y., Gräber, S., Kovacs, I., Lee, W.D., Waggoner, J., Cui, J., White, A.D., Bossy, B., Martinou, J.C., Youle, R.J., Lipton, S.A., Ellisman, M.H., Perkins, G.A., Bossy-Wetzel, E. EMBO J. (2006) [Pubmed]
  18. Drp-1-dependent division of the mitochondrial network blocks intraorganellar Ca2+ waves and protects against Ca2+-mediated apoptosis. Szabadkai, G., Simoni, A.M., Chami, M., Wieckowski, M.R., Youle, R.J., Rizzuto, R. Mol. Cell (2004) [Pubmed]
  19. Human Ku autoantigen binds cisplatin-damaged DNA but fails to stimulate human DNA-activated protein kinase. Turchi, J.J., Henkels, K. J. Biol. Chem. (1996) [Pubmed]
  20. Regulators of GTP-binding proteins cause morphological changes in the vacuole system of the filamentous fungus, Pisolithus tinctorius. Hyde, G.J., Davies, D., Cole, L., Ashford, A.E. Cell Motil. Cytoskeleton (2002) [Pubmed]
  21. Cyclic AMP-dependent protein kinase phosphorylation of Drp1 regulates its GTPase activity and mitochondrial morphology. Chang, C.R., Blackstone, C. J. Biol. Chem. (2007) [Pubmed]
  22. Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death. Cribbs, J.T., Strack, S. EMBO Rep. (2007) [Pubmed]
  23. Plakophilin 3 oncogene as prognostic marker and therapeutic target for lung cancer. Furukawa, C., Daigo, Y., Ishikawa, N., Kato, T., Ito, T., Tsuchiya, E., Sone, S., Nakamura, Y. Cancer Res. (2005) [Pubmed]
  24. The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1. Yoon, Y., Krueger, E.W., Oswald, B.J., McNiven, M.A. Mol. Cell. Biol. (2003) [Pubmed]
  25. Dynasore, a cell-permeable inhibitor of dynamin. Macia, E., Ehrlich, M., Massol, R., Boucrot, E., Brunner, C., Kirchhausen, T. Dev. Cell (2006) [Pubmed]
  26. Peroxisome elongation and constriction but not fission can occur independently of dynamin-like protein 1. Koch, A., Schneider, G., Lüers, G.H., Schrader, M. J. Cell. Sci. (2004) [Pubmed]
  27. Mitochondrial fission proteins regulate programmed cell death in yeast. Fannjiang, Y., Cheng, W.C., Lee, S.J., Qi, B., Pevsner, J., McCaffery, J.M., Hill, R.B., Basañez, G., Hardwick, J.M. Genes Dev. (2004) [Pubmed]
  28. Regulation of mitochondrial fission and apoptosis by the mitochondrial outer membrane protein hFis1. Yu, T., Fox, R.J., Burwell, L.S., Yoon, Y. J. Cell. Sci. (2005) [Pubmed]
  29. Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Smirnova, E., Griparic, L., Shurland, D.L., van der Bliek, A.M. Mol. Biol. Cell (2001) [Pubmed]
  30. Identification and functional characterization of a novel human protein highly related to the yeast dynamin-like GTPase Vps1p. Imoto, M., Tachibana, I., Urrutia, R. J. Cell. Sci. (1998) [Pubmed]
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