SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle

FASEB Journal

Volumn 23, Issue 11, 2009, Pages 3917-3927

  Figueroa Romero, Claudia ^a   Iñiguez Lluhí, Jorge A ^a   Stadler, Julia ^b   Chang, Chuang Rung ^b   Arnoult, Damien ^c   Keller, Peter J ^a   Hong, Yu ^a   Blackstone, Craig ^b   Feldman, Eva L ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE   (United States)

^c INSERM   (France)

Author keywords

Post translational modification; Small ubiquitin like modifier; Ubc9

Indexed keywords

DYNAMIN RELATED PROTEIN 1; GUANINE NUCLEOTIDE BINDING PROTEIN; GUANOSINE TRIPHOSPHATASE; HYBRID PROTEIN; ISOPROTEIN; LEXA PROTEIN; LYSINE; PROTEIN SUMO 3; PROTEIN UBC9; STAUROSPORINE; SUMO 1 PROTEIN; SUMO 2 PROTEIN; UNCLASSIFIED DRUG;

ARTICLE; CELL STRAIN HEK293; CONTROLLED STUDY; HELA CELL; HUMAN; HUMAN CELL; HYDROLYSIS; MITOCHONDRION; MUTATIONAL ANALYSIS; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN MODIFICATION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; PROTEIN VARIANT; SACCHAROMYCES CEREVISIAE; SUMOYLATION;

ACYLATION; CELLS, CULTURED; GTP PHOSPHOHYDROLASES; HUMANS; MICROTUBULE-ASSOCIATED PROTEINS; MITOCHONDRIAL PROTEINS; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEIN STRUCTURE, TERTIARY; SMALL UBIQUITIN-RELATED MODIFIER PROTEINS; UBIQUITIN-CONJUGATING ENZYMES;

EID: 70350543964     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.09-136630     Document Type: Article

References (83)

1. Cerveny, K. L., Tamura, Y., Zhang, Z., Jensen, R. E., and Sesaki, H. (2007) Regulation of mitochondrial fusion and division. Trends Cell Biol. 17, 563-569
2. Griparic, L., van der Wel, N. N., Orozco, I. J., Peters, P. J., and van der Bliek, A. M. (2004) Loss of the intermembrane space protein Mgm1/OPA1 induces swelling and localized constrictions along the lengths of mitochondria. J. Biol. Chem. 279, 18792-18798 (Pubitemid 38623305)
3. Santel, A., Frank, S., Gaume, B., Herrler, M., Youle, R. J., and Fuller, M. T. (2003) Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells. J. Cell Sci. 116, 2763-2774 (Pubitemid 36857227)
4. Wells, R. C., Picton, L. K., Williams, S. C., Tan, F. J., and Hill, R. B. (2007) Direct binding of the dynamin-like GTPase, Dnm1, to mitochondrial dynamics protein Fis1 is negatively regulated by the Fis1 N-terminal arm. J. Biol. Chem. 282, 33769-33775
5. Yoon, Y., Krueger, E. W., Oswald, B. J., and McNiven, M. A. (2003) The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1. Mol. Cell. Biol. 23, 5409-5420 (Pubitemid 36950895)
6. Mozdy, A. D., McCaffery, J. M., and Shaw, J. M. (2000) Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p. J. Cell Biol. 151, 367-380
7. Chen, H., and Chan, D. C. (2006) Critical dependence of neurons on mitochondrial dynamics. Curr. Opin. Cell Biol. 18, 453-459 (Pubitemid 44016054)
8. Baloh, R. H. (2008) Mitochondrial dynamics and peripheral neuropathy. Neuroscientist 14, 12-18
9. Chan, D. C. (2007) Mitochondrial dynamics in disease. N. Engl. J. Med. 356, 1707-1709
10. Ghafourifar, P., Mousavizadeh, K., Parihar, M. S., Nazarewicz, R. R., Parihar, A., and Zenebe, W. J. (2008) Mitochondria in multiple sclerosis. Front. Biosci. 13, 3116-3126
11. Zeviani, M., and Carelli, V. (2007) Mitochondrial disorders. Curr. Opin. Neurol. 20, 564-571
12. 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., and Wissinger, B. (2000) OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Nat. Genet. 26, 211-215 (Pubitemid 30764506)
13. 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., and Hamel, C. P. (2000) Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat. Genet. 26, 207-210 (Pubitemid 30764505)
14. Zuchner, S., Mersiyanova, I. V., Muglia, M., Bissar-Tadmouri, N., Rochelle, J., Dadali, E. L., Zappia, M., Nelis, E., Patitucci, A., Senderek, J., Parman, Y., Evgrafov, O., Jonghe, P. D., Takahashi, Y., Tsuji, S., Pericak-Vance, M. A., Quattrone, A., Battaloglu, E., Polyakov, A. V., Timmerman, V., Schroder, J. M., and Vance, J. M. (2004) Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat. Genet. 36, 449-451 (Pubitemid 38620027)
15. Waterham, H. R., Koster, J., van Roermund, C. W., Mooyer, P. A., Wanders, R. J., and Leonard, J. V. (2007) A lethal defect of mitochondrial and peroxisomal fission. N. Engl. J. Med. 356, 1736-1741 (Pubitemid 46658705)
16. Zhu, P. P., Patterson, A., Stadler, J., Seeburg, D. P., Sheng, M., and Blackstone, C. (2004) Intra- and intermolecular domain interactions of the C-terminal GTPase effector domain of the multimeric dynamin-like GTPase Drp1. J. Biol. Chem. 279, 35967-35974 (Pubitemid 39100604)
17. Ingerman, E., Perkins, E. M., Marino, M., Mears, J. A., McCaffery, J. M., Hinshaw, J. E., and Nunnari, J. (2005) Dnm1 forms spirals that are structurally tailored to fit mitochondria. J. Cell Biol. 170, 1021-1027 (Pubitemid 41362634)
18. Smirnova, E., Griparic, L., Shurland, D. L., and van der Bliek, A. M. (2001) Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Mol. Biol. Cell 12, 2245-2256 (Pubitemid 33051954)
19. Smirnova, E., Shurland, D. L., Ryazantsev, S. N., and van der Bliek, A. M. (1998) A human dynamin-related protein controls the distribution of mitochondria. J. Cell Biol. 143, 351-358 (Pubitemid 28487855)
20. Cassidy-Stone, A., Chipuk, J. E., Ingerman, E., Song, C., Yoo, C., Kuwana, T., Kurth, M. J., Shaw, J. T., Hinshaw, J. E., Green, D. R., and Nunnari, J. (2008) Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization. Dev. Cell. 14, 193-204 (Pubitemid 351189177)
21. Etxebarria, A., Terrones, O., Yamaguchi, H., Landajuela, A., Landeta, O., Antonsson, B., Wang, H. G., and Basanez, G. (2009) Endophilin B1/Bif-1 stimulates BAX activation independently from its capacity to produce large-scale membrane morphological rearrangements. J. Biol. Chem. 284, 4200-4212
22. Frank, S., Gaume, B., Bergmann-Leitner, E. S., Leitner, W. W., Robert, E. G., Catez, F., Smith, C. L., and Youle, R. J. (2001) The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev. Cell. 1, 515-525 (Pubitemid 33586103)
23. Cereghetti, G. M., Stangherlin, A., Martins de Brito, O., Chang, C. R., Blackstone, C., Bernardi, P., and Scorrano, L. (2008) Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria. Proc. Natl. Acad. Sci. U. S. A. 105, 15803-15808
24. Chang, C. R., and Blackstone, C. (2007) Cyclic AMP-dependent protein kinase phosphorylation of Drp1 regulates its GTPase activity and mitochondrial morphology. J. Biol. Chem. 282, 21583-21587 (Pubitemid 47195725)
25. Cho, D. H., Nakamura, T., Fang, J., Cieplak, P., Godzik, A., Gu, Z., and Lipton, S. A. (2009) S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury. Science 324, 102-105
26. Cribbs, J. T., and Strack, S. (2007) Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death. EMBO Rep. 8, 939-944 (Pubitemid 47500477)
27. Han, X. J., Lu, Y. F., Li, S. A., Kaitsuka, T., Sato, Y., Tomizawa, K., Nairn, A. C., Takei, K., Matsui, H., and Matsushita, M. (2008) CaM kinase I alpha-induced phosphorylation of Drp1 regulates mitochondrial morphology. J. Cell Biol. 182, 573-585
28. Harder, Z., Zunino, R., and McBride, H. (2004) Sumo1 conjugates mitochondrial substrates and participates in mitochondrial fission. Curr. Biol. 14, 340-345 (Pubitemid 38300214)
29. Nakamura, N., Kimura, Y., Tokuda, M., Honda, S., and Hirose, S. (2006) MARCH-V is a novel mitofusin 2- and Drp1-binding protein able to change mitochondrial morphology. EMBO Rep. 7, 1019-1022 (Pubitemid 44480517)
30. Taguchi, N., Ishihara, N., Jofuku, A., Oka, T., and Mihara, K. (2007) Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission. J. Biol. Chem. 282, 11521-11529 (Pubitemid 47100787)
31. Wasiak, S., Zunino, R., and McBride, H. M. (2007) Bax/Bak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death. J. Cell Biol. 177, 439-450 (Pubitemid 46718273)
32. Zunino, R., Schauss, A., Rippstein, P., Andrade-Navarro, M., and McBride, H. M. (2007) The SUMO protease SENP5 is required to maintain mitochondrial morphology and function. J. Cell Sci. 120, 1178-1188 (Pubitemid 46711836)
33. Ulrich, H. D. (2005) Mutual interactions between the SUMO and ubiquitin systems: a plea of no contest. Trends Cell Biol. 15, 525-532
34. Saitoh, H., and Hinchey, J. (2000) Functional heterogeneity of small ubiquitin-related protein modifiers SUMO-1 versus SUMO-2/3. J. Biol. Chem. 275, 6252-6258 (Pubitemid 30129915)
35. Su, H. L., and Li, S. S. (2002) Molecular features of human ubiquitin-like SUMO genes and their encoded proteins. Gene 296, 65-73
36. Bohren, K. M., Nadkarni, V., Song, J. H., Gabbay, K. H., and Owerbach, D. (2004) A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus. J. Biol. Chem. 279, 27233-27238 (Pubitemid 38812561)
37. Owerbach, D., McKay, E. M., Yeh, E. T., Gabbay, K. H., and Bohren, K. M. (2005) A proline-90 residue unique to SUMO-4 prevents maturation and sumoylation. Biochem. Biophys. Res. Commun. 337, 517-520 (Pubitemid 41429315)
38. Sampson, D. A., Wang, M., and Matunis, M. J. (2001) The small ubiquitin-like modifier-1 (SUMO-1) consensus sequence mediates Ubc9 binding and is essential for SUMO-1 modification. J. Biol. Chem. 276, 21664-21669 (Pubitemid 37413167)
39. Chun, T. H., Itoh, H., Subramanian, L., Iniguez-Lluhi, J. A., and Nakao, K. (2003) Modification of GATA-2 transcriptional activity in endothelial cells by the SUMO E3 ligase PIASy. Circ. Res. 92, 1201-1208 (Pubitemid 36723647)
40. Pichler, A., Gast, A., Seeler, J. S., Dejean, A., and Melchior, F. (2002) The nucleoporin RanBP2 has SUMO1 E3 ligase activity. Cell 108, 109-120 (Pubitemid 34137016)
41. Sachdev, S., Bruhn, L., Sieber, H., Pichler, A., Melchior, F., and Grosschedl, R. (2001) PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activity by sequestration into nuclear bodies. Genes Dev. 15, 3088-3103 (Pubitemid 33115674)
42. Yeh, E. T., Gong, L., and Kamitani, T. (2000) Ubiquitin-like proteins: new wines in new bottles. Gene 248, 1-14 (Pubitemid 30259196)
43. Chupreta, S., Holmstrom, S., Subramanian, L., and Iniguez- Lluhi, J. A. (2005) A small conserved surface in SUMO is the critical structural determinant of its transcriptional inhibitory properties. Mol. Cell. Biol. 25, 4272-4282
44. Song, J., Durrin, L. K., Wilkinson, T. A., Krontiris, T. G., and Chen, Y. (2004) Identification of a SUMO-binding motif that recognizes SUMO-modified proteins. Proc. Natl. Acad. Sci. U. S. A. 101, 14373-14378 (Pubitemid 39346756)
45. Benson, M. D., Li, Q. J., Kieckhafer, K., Dudek, D., Whorton, M. R., Sunahara, R. K., Iniguez-Lluhi, J. A., and Martens, J. R. (2007) SUMO modification regulates inactivation of the voltage-gated potassium channel Kv1.5. Proc. Natl. Acad. Sci. U. S. A. 104, 1805-1810 (Pubitemid 46239860)
46. Vojtek, A. B., Hollenberg, S. M., and Cooper, J. A. (1993) Mammalian Ras interacts directly with the serine/threonine kinase Raf. Cell 74, 205-214 (Pubitemid 23219891)
47. Arnoult, D., Grodet, A., Lee, Y. J., Estaquier, J., and Blackstone, C. (2005) Release of OPA1 during apoptosis participates in the rapid and complete release of cytochrome c and subsequent mitochondrial fragmentation. J. Biol. Chem. 280, 35742-35750 (Pubitemid 41532767)
48. Arnoult, D., Rismanchi, N., Grodet, A., Roberts, R. G., Seeburg, D. P., Estaquier, J., Sheng, M., and Blackstone, C. (2005) Bax/Bak-dependent release of DDP/TIMM8a promotes Drp1-mediated mitochondrial fission and mitoptosis during programmed cell death. Curr. Biol. 15, 2112-2118 (Pubitemid 41739743)
49. Santel, A., and Frank, S. (2008) Shaping mitochondria: The complex posttranslational regulation of the mitochondrial fission protein DRP1. IUBMB Life 60, 448-455
50. Bernier-Villamor, V., Sampson, D. A., Matunis, M. J., and Lima, C. D. (2002) Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1. Cell 108, 345-356 (Pubitemid 34178399)
51. Rodriguez, M. S., Dargemont, C., and Hay, R. T. (2001) SUMO-1 conjugation in vivo requires both a consensus modification motif and nuclear targeting. J. Biol. Chem. 276, 12654-12659 (Pubitemid 37385176)
52. Kamimoto, T., Nagai, Y., Onogi, H., Muro, Y., Wakabayashi, T., and Hagiwara, M. (1998) Dymple, a novel dynamin-like high molecular weight GTPase lacking a proline-rich carboxyl-terminal domain in mammalian cells. J. Biol. Chem. 273, 1044-1051 (Pubitemid 28049202)
53. Niemann, H. H., Knetsch, M. L., Scherer, A., Manstein, D. J., and Kull, F. J. (2001) Crystal structure of a dynamin GTPase domain in both nucleotide-free and GDP-bound forms. EMBO J. 20, 5813-5821 (Pubitemid 33049257)
54. Germain, M., Mathai, J. P., McBride, H. M., and Shore, G. C. (2005) Endoplasmic reticulum BIK initiates DRP1-regulated remodelling of mitochondrial cristae during apoptosis. EMBO J. 24, 1546-1556 (Pubitemid 40646445)
55. Schrader, M. (2006) Shared components of mitochondrial and peroxisomal division. Biochim. Biophys. Acta 1763, 531-541
56. Shin, H. W., Shinotsuka, C., Torii, S., Murakami, K., and Nakayama, K. (1997) Identification and subcellular localization of a novel mammalian dynamin-related protein homologous to yeast Vps1p and Dnm1p. J. Biochem. 122, 525-530 (Pubitemid 27443227)
57. Li, M., Guo, D., Isales, C. M., Eizirik, D. L., Atkinson, M., She, J. X., and Wang, C. Y. (2005) SUMO wrestling with type 1 diabetes. J. Mol. Med. 83, 504-513
58. Dorval, V., and Fraser, P. E. (2007) SUMO on the road to neurodegeneration. Biochim. Biophys. Acta 1773, 694-706
59. Matic, I., van Hagen, M., Schimmel, J., Macek, B., Ogg, S. C., Tatham, M. H., Hay, R. T., Lamond, A. I., Mann, M., and Vertegaal, A. C. (2008) In vivo identification of human small ubiquitin-like modifier polymerization sites by high accuracy mass spectrometry and an in vitro to in vivo strategy. Mol. Cell. Proteomics 7, 132-144 (Pubitemid 351248239)
60. Zhang, F. P., Mikkonen, L., Toppari, J., Palvimo, J. J., Thesleff, I., and Janne, O. A. (2008) Sumo-1 function is dispensable in normal mouse development. Mol. Cell. Biol. 28, 5381-5390
61. Ulrich, H. D. (2008) The fast-growing business of SUMO chains. Mol. Cell. 32, 301-305
62. Tatham, M. H., Jaffray, E., Vaughan, O. A., Desterro, J. M., Botting, C. H., Naismith, J. H., and Hay, R. T. (2001) Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9. J. Biol. Chem. 276, 35368-35374 (Pubitemid 37384330)
63. Lin, D. Y., Huang, Y. S., Jeng, J. C., Kuo, H. Y., Chang, C. C., Chao, T. T., Ho, C. C., Chen, Y. C., Lin, T. P., Fang, H. I., Hung, C. C., Suen, C. S., Hwang, M. J., Chang, K. S., Maul, G. G., and Shih, H. M. (2006) Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors. Mol. Cell. 24, 341-354
64. Ivanov, A. V., Peng, H., Yurchenko, V., Yap, K. L., Negorev, D. G., Schultz, D. C., Psulkowski, E., Fredericks, W. J., White, D. E., Maul, G. G., Sadofsky, M. J., Zhou, M. M., and Rauscher, F. J., 3rd (2007) PHD domain-mediated E3 ligase activity directs intramolecular sumoylation of an adjacent bromodomain required for gene silencing. Mol. Cell. 28, 823-837
65. Zunino, R., Braschi, E., Xu, L., and McBride, H. M. (2009) Translocation of SenP5 from the nucleoli to the mitochondria modulates DRP1-dependent fission during mitosis. J. Biol. Chem. 284, 17783-17795
66. Braschi, E., Zunino, R., and McBride, H. M. (2009) MAPL is a new mitochondrial SUMO E3 ligase that regulates mitochondrial fission. EMBO Rep. 10, 748-754
67. Van der Bliek, A. M., Redelmeier, T. E., Damke, H., Tisdale, E. J., Meyerowitz, E. M., and Schmid, S. L. (1993) Mutations in human dynamin block an intermediate stage in coated vesicle formation. J. Cell Biol. 122, 553-563 (Pubitemid 23226673)
68. Vater, C. A., Raymond, C. K., Ekena, K., Howald-Stevenson, I., and Stevens, T. H. (1992) The VPS1 protein, a homolog of dynamin required for vacuolar protein sorting in Saccharomyces cerevisiae, is a GTPase with two functionally separable domains. J. Cell Biol. 119, 773-786
69. Damke, H., Baba, T., Warnock, D. E., and Schmid, S. L. (1994) Induction of mutant dynamin specifically blocks endocytic coated vesicle formation. J. Cell Biol. 127, 915-934 (Pubitemid 24355982)
70. Bleazard, W., McCaffery, J. M., King, E. J., Bale, S., Mozdy, A., Tieu, Q., Nunnari, J., and Shaw, J. M. (1999) The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast. Nat. Cell Biol. 1, 298-304 (Pubitemid 129495781)
71. Labrousse, A. M., Zappaterra, M. D., Rube, D. A., and van der Bliek, A. M. (1999) C. elegans dynamin-related protein DRP-1 controls severing of the mitochondrial outer membrane. Mol. Cell. 4, 815-826
72. Pitts, K. R., Yoon, Y., Krueger, E. W., and McNiven, M. A. (1999) The dynamin-like protein DLP1 is essential for normal distribution and morphology of the endoplasmic reticulum and mitochondria in mammalian cells. Mol. Biol. Cell. 10, 4403-4417
73. Yoon, Y., Pitts, K. R., and McNiven, M. A. (2001) Mammalian dynamin-like protein DLP1 tubulates membranes. Mol. Biol. Cell. 12, 2894-2905 (Pubitemid 33051952)
74. Yu, T., Sheu, S. S., Robotham, J. L., and Yoon, Y. (2008) Mitochondrial fission mediates high glucose-induced cell death through elevated production of reactive oxygen species. Cardiovasc. Res. 79, 341-351 (Pubitemid 351951612)
75. Johnson, E. S., and Blobel, G. (1999) Cell cycle-regulated attachment of the ubiquitin-related protein SUMO to the yeast septins. J. Cell Biol. 147, 981-994
76. Pountney, D. L., Raftery, M. J., Chegini, F., Blumbergs, P. C., and Gai, W. P. (2008) NSF, Unc-18-1, dynamin-1 and HSP90 are inclusion body components in neuronal intranuclear inclusion disease identified by anti-SUMO-1- immunocapture. Acta Neuropathol. 116, 603-614
77. Mishra, R. K., Jatiani, S. S., Kumar, A., Simhadri, V. R., Hosur, R. V., and Mittal, R. (2004) Dynamin interacts with members of the sumoylation machinery. J. Biol. Chem. 279, 31445-31454 (Pubitemid 39037812)
78. Leinninger, G. M., Backus, C., Sastry, A. M., Yi, Y. B., Wang, C. W., and Feldman, E. L. (2006) Mitochondria in DRG neurons undergo hyperglycemic mediated injury through Bim, Bax and the fission protein Drp1. Neurobiol. Dis. 23, 11-22 (Pubitemid 44192383)
79. Wang, X., Su, B., Fujioka, H., and Zhu, X. (2008) Dynamin-like protein 1 reduction underlies mitochondrial morphology and distribution abnormalities in fibroblasts from sporadic Alzheimer's disease patients. Am. J. Pathol. 173, 470-482
80. Yang, Y., Ouyang, Y., Yang, L., Beal, M. F., McQuibban, A., Vogel, H., and Lu, B. (2008) Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery. Proc. Natl. Acad. Sci. U. S. A. 105, 7070-7075 (Pubitemid 351754531)
81. Men, X., Wang, H., Li, M., Cai, H., Xu, S., Zhang, W., Xu, Y., Ye, L., Yang, W., Wollheim, C. B., and Lou, J. (2009) Dynamin-related protein 1 mediates high glucose induced pancreatic beta cell apoptosis. Int. J. Biochem. Cell Biol. 41, 879-890
82. Mukherjee, S., Thomas, M., Dadgar, N., Lieberman, A. P., and Iniguez-Lluhl, J. A. (2009) SUMO modification of the androgen receptor attenuates polyglutamine-mediated aggregation. J. Biol. Chem., M109.011494
83. Subramaniam, S., Sixt, K. M., Barrow, R., and Snyder, S. H. (2009) Rhes, a striatal specific protein, mediates mutant-huntingtin cytotoxicity. Science 324, 1327-1330