A novel Drp1 inhibitor diminishes aberrant mitochondrial fission and neurotoxicity

Journal of Cell Science

Volumn 126, Issue 3, 2013, Pages 789-802

  Qi, Xin ^a   Qvit, Nir ^b   Su, Yu Chin ^a   Mochly Rosen, Daria ^b  

^a CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Dynamin related protein 1; Mitochondrial fission; Neuronal cell death; Peptide inhibitor

Indexed keywords

CELL PROTEIN; DRP1 PROTEIN; DYNAMIN; FIS1 PROTEIN; PROTEIN INHIBITOR; PROTEIN P110; REACTIVE OXYGEN METABOLITE; RECOMBINANT PROTEIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; AUTOPHAGY; CELL DEATH; CELL LOSS; CELL VIABILITY; CONTROLLED STUDY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DOPAMINERGIC NERVE CELL; ENZYME ACTIVITY; ENZYME INHIBITION; FRAGMENTATION REACTION; HUMAN; HUMAN CELL; IMMUNOPRECIPITATION; IN VITRO STUDY; MITOCHONDRIAL FISSION; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRION; MOUSE; NERVE CELL CULTURE; NEURITE; NEUROPROTECTION; NEUROTOXICITY; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PEPTIDE SYNTHESIS; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION;

APOPTOSIS; AUTOPHAGY; CELL LINE; DOPAMINERGIC NEURONS; ENZYME INHIBITORS; GENE KNOCKOUT TECHNIQUES; GTP PHOSPHOHYDROLASES; HUMANS; MEMBRANE POTENTIAL, MITOCHONDRIAL; MICROTUBULE-ASSOCIATED PROTEINS; MITOCHONDRIA; MITOCHONDRIAL DYNAMICS; MITOCHONDRIAL PROTEINS; MOLECULAR TARGETED THERAPY; NEUROPROTECTIVE AGENTS; OXIDATIVE STRESS; OXIDOREDUCTASES; PARKINSON DISEASE; PEPTIDE FRAGMENTS; PLANT PROTEINS; REACTIVE OXYGEN SPECIES; TRANSGENES;

EID: 84876312885     PISSN: 00219533     EISSN: 14779137     Source Type: Journal    
DOI: 10.1242/jcs.114439     Document Type: Article

References (60)

1. Barsoum, M. J., Yuan, H., Gerencser, A. A., Liot, G., Kushnareva, Y., Gräber, S., Kovacs, I., Lee, W. D., Waggoner, J., Cui, J. et al. (2006). Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons. EMBO J. 25, 3900-3911.
2. Begley, R., Liron, T., Baryza, J. and Mochly-Rosen, D. (2004). Biodistribution of intracellularly acting peptides conjugated reversibly to Tat. Biochem. Biophys. Res. Commun. 318, 949-954.
3. Bright, R., Raval, A. P., Dembner, J. M., Pérez-Pinzón, M. A., Steinberg, G. K., Yenari, M. A. and Mochly-Rosen, D. (2004). Protein kinase C delta mediates cerebral reperfusion injury in vivo. J. Neurosci. 24, 6880-6888.
4. Brunel, F. M., Zwick, M. B., Cardoso, R. M., Nelson, J. D., Wilson, I. A., Burton, D. R. and Dawson, P. E. (2006). Structure-function analysis of the epitope for 4E10, a broadly neutralizing human immunodeficiency virus type 1 antibody. J. Virol. 80, 1680-1687.
5. Büeler, H. (2009). Impaired mitochondrial dynamics and function in the pathogenesis of Parkinson's disease. Exp. Neurol. 218, 235-246.
6. 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. et al. (2008). Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bakdependent mitochondrial outer membrane permeabilization. Dev. Cell 14, 193-204.
7. Chan, D. C. (2006a). Mitochondria: dynamic organelles in disease, aging, and development. Cell 125, 1241-1252.
8. Chan, D. C. (2006b). Mitochondrial fusion and fission in mammals. Annu. Rev. Cell Dev. Biol. 22, 79-99.
9. Chang, C. R. and Blackstone, C. (2010). Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1. Ann. N. Y. Acad. Sci. 1201, 34-39.
10. Chen, L., Hahn, H., Wu, G., Chen, C. H., Liron, T., Schechtman, D., Cavallaro, G., Banci, L., Guo, Y., Bolli, R. et al. (2001a). Opposing cardioprotective actions and parallel hypertrophic effects of delta PKC and epsilon PKC. Proc. Natl. Acad. Sci. USA 98, 11114-11119.
11. Chen, L., Wright, L. R., Chen, C. H., Oliver, S. F., Wender, P. A. and Mochly-Rosen, D. (2001b). Molecular transporters for peptides: delivery of a cardioprotective epsilonPKC agonist peptide into cells and intact ischemic heart using a transport system, R(7). Chem. Biol. 8, 1123-1129.
12. Dorn, G. W., 2nd, Souroujon, M. C., Liron, T., Chen, C. H., Gray, M. O., Zhou, H. Z., Csukai, M., Wu, G., Lorenz, J. N. and Mochly-Rosen, D. (1999). Sustained in vivo cardiac protection by a rationally designed peptide that causes epsilon protein kinase C translocation. Proc. Natl. Acad. Sci. USA 96, 12798-12803.
13. Estaquier, J. and Arnoult, D. (2007). Inhibiting Drp1-mediated mitochondrial fission selectively prevents the release of cytochrome c during apoptosis. Cell Death Differ. 14, 1086-1094.
14. Fannjiang, Y., Cheng, W. C., Lee, S. J., Qi, B., Pevsner, J., McCaffery, J. M., Hill, R. B., Basañez, G. and Hardwick, J. M. (2004). Mitochondrial fission proteins regulate programmed cell death in yeast. Genes Dev. 18, 2785-2797.
15. Ferrari, L. F., Chum, A., Bogen, O., Reichling, D. B. and Levine, J. D. (2011). Role of Drp1, a key mitochondrial fission protein, in neuropathic pain. J. Neurosci. 31, 11404-11410.
16. 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.
17. Hájek, P., Chomyn, A. and Attardi, G. (2007). Identification of a novel mitochondrial complex containing mitofusin 2 and stomatin-like protein 2. J. Biol. Chem. 282, 5670-5681.
18. Huang, X. and Miller, W. (1991). Time-efficient, linear-space local similarity algorithm. Adv. Appl. Math. 12, 337-357.
19. Inagaki, K., Chen, L., Ikeno, F., Lee, F. H., Imahashi, K., Bouley, D. M., Rezaee, M., Yock, P. G., Murphy, E. and Mochly-Rosen, D. (2003). Inhibition of delta-protein kinase C protects against reperfusion injury of the ischemic heart in vivo. Circulation 108, 2304-2307.
20. Inagaki, K., Koyanagi, T., Berry, N. C., Sun, L. and Mochly-Rosen, D. (2008). Pharmacological inhibition of epsilon-protein kinase C attenuates cardiac fibrosis and dysfunction in hypertension-induced heart failure. Hypertension 51, 1565-1569.
21. 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.
22. Jahani-Asl, A., Germain, M. and Slack, R. S. (2010). Mitochondria: joining forces to thwart cell death. Biochim. Biophys. Acta 1802, 162-166.
23. James, D. I., Parone, P. A., Mattenberger, Y. and Martinou, J. C. (2003). hFis1, a novel component of the mammalian mitochondrial fission machinery. J. Biol. Chem. 278, 36373-36379.
24. Johnson-Cadwell, L. I., Jekabsons, M. B., Wang, A., Polster, B. M. and Nicholls, D. G. (2007). 'Mild Uncoupling' does not decrease mitochondrial superoxide levels in cultured cerebellar granule neurons but decreases spare respiratory capacity and increases toxicity to glutamate and oxidative stress. J. Neurochem. 101, 1619-1631.
25. Kheifets, V., Bright, R., Inagaki, K., Schechtman, D. and Mochly-Rosen, D. (2006). Protein kinase C delta (deltaPKC)-annexin V interaction: a required step in deltaPKC translocation and function. J. Biol. Chem. 281, 23218-23226.
26. Kim, K. Y. and Sack, M. N. (2012). Parkin in the regulation of fat uptake and mitochondrial biology: emerging links in the pathophysiology of Parkinson's disease. Curr. Opin. Lipidol. 23, 201-205.
27. Kim, J., Koyanagi, T. and Mochly-Rosen, D. (2011). PKCd activation mediates angiogenesis via NADPH oxidase activity in PC-3 prostate cancer cells. Prostate 71, 946-954.
28. Knott, A. B., Perkins, G., Schwarzenbacher, R. and Bossy-Wetzel, E. (2008). Mitochondrial fragmentation in neurodegeneration. Nat. Rev. Neurosci. 9, 505-518.
29. Lichtarge, O., Bourne, H. R. and Cohen, F. E. (1996). An evolutionary trace method defines binding surfaces common to protein families. J. Mol. Biol. 257, 342-358.
30. Liu, W., Tian, F., Kurata, T., Morimoto, N. and Abe, K. (2012). Dynamic changes of mitochondrial fission proteins after transient cerebral ischemia in mice. Brain Res. 1456, 94-99.
31. Mammucari, C. and Rizzuto, R. (2010). Signaling pathways in mitochondrial dysfunction and aging. Mech. Ageing Dev. 131, 536-543.
32. McClure, S. J. and Robinson, P. J. (1996). Dynamin, endocytosis and intracellular signalling (review). Mol. Membr. Biol. 13, 189-215.
33. Miyaji, Y., Walter, S., Chen, L., Kurihara, A., Ishizuka, T., Saito, M., Kawai, K. and Okazaki, O. (2011). Distribution of KAI-9803, a novel d-protein kinase C inhibitor, after intravenous administration to rats. Drug Metab. Dispos. 39, 1946-1953.
34. Onoue, K., Jofuku, A., Ban-Ishihara, R., Ishihara, T., Maeda, M., Koshiba, T., Itoh, T., Fukuda, M., Otera, H., Oka, T. et al. (2012). Fis1 acts as mitochondrial recruitment factor for TBC1D15 that involved in regulation of mitochondrial morphology. J. Cell Sci. 126, 176-185.
35. Otera, H., Wang, C., Cleland, M. M., Setoguchi, K., Yokota, S., Youle, R. J. and Mihara, K. (2010). Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells. J. Cell Biol. 191, 1141-1158.
36. Palaniyandi, S. S., Sun, L., Ferreira, J. C. and Mochly-Rosen, D. (2009). Protein kinase C in heart failure: a therapeutic target? Cardiovasc. Res. 82, 229-239.
37. Palaniyandi, S. S., Qi, X., Yogalingam, G., Ferreira, J. C. and Mochly-Rosen, D. (2010). Regulation of mitochondrial processes: a target for heart failure. Drug Discov. Today Dis. Mech. 7, e95-e102.
38. Palmer, C. S., Osellame, L. D., Laine, D., Koutsopoulos, O. S., Frazier, A. E. and Ryan, M. T. (2011). MiD49 and MiD51, new components of the mitochondrial fission machinery. EMBO Rep. 12, 565-573.
39. Qi,X., Inagaki, K., Sobel, R. A. andMochly-Rosen, D. (2008). Sustained pharmacological inhibition of deltaPKC protects against hypertensive encephalopathy through prevention of blood-brain barrier breakdown in rats. J. Clin. Invest. 118, 173-182.
40. Qi, X., Disatnik, M. H., Shen, N., Sobel, R. A. and Mochly-Rosen, D. (2011). Aberrant mitochondrial fission in neurons induced by protein kinase Cdelta under oxidative stress conditions in vivo. Mol. Biol. Cell 22, 256-265.
41. Qvit, N. and Mochly-Rosen, D. (2010). Highly specific modulators of protein kinase C localization: applications to heart failure. Drug Discov. Today Dis. Mech. 7, e87-e93.
42. Reddy, P. H., Reddy, T. P., Manczak, M., Calkins, M. J., Shirendeb, U. and Mao, P. (2011). Dynamin-related protein 1 and mitochondrial fragmentation in neurodegenerative diseases. Brain Res. Rev. 67, 103-118.
43. Rolo, A. P., Gomes, A. P. and Palmeira, C. M. (2011). Regulation of mitochondrial biogenesis in metabolic syndrome. Curr. Drug Targets 12, 872-878.
44. Ron, D. and Mochly-Rosen, D. (1995). An autoregulatory region in protein kinase C: the pseudoanchoring site. Proc. Natl. Acad. Sci. USA 92, 492-496.
45. Sabatino, G. and Papini, A. M. (2008). Advances in automatic, manual and microwave-assisted solid-phase peptide synthesis. Curr. Opin. Drug Discov. Devel. 11, 762-770.
46. Scott, I. and Youle, R. J. (2010). Mitochondrial fission and fusion. Essays Biochem. 47, 85-98.
47. 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.
48. Souroujon, M. C. and Mochly-Rosen, D. (1998). Peptide modulators of protein-protein interactions in intracellular signaling. Nat. Biotechnol. 16, 919-924.
49. Suzuki, M., Neutzner, A., Tjandra, N. and Youle, R. J. (2005). Novel structure of the N terminus in yeast Fis1 correlates with a specialized function in mitochondrial fission. J. Biol. Chem. 280, 21444-21452.
50. Sweitzer, S. M., Wong, S. M., Tjolsen, A., Allen, C. P., Mochly-Rosen, D. and Kendig, J. J. (2004). Exaggerated nociceptive responses on morphine withdrawal: roles of protein kinase C epsilon and gamma. Pain 110, 281-289.
51. Tamura, K., Peterson, D., Peterson, N., Stecher, G., Nei, M. and Kumar, S. (2011). MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol. Biol. Evol. 28, 2731-2739.
52. Twig, G., Elorza, A., Molina, A. J., Mohamed, H., Wikstrom, J. D., Walzer, G., Stiles, L., Haigh, S. E., Katz, S., Las, G. et al. (2008). Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J. 27, 433-446.
53. Wang, Z., Jiang, H., Chen, S., Du, F. and Wang, X. (2012). The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell 148, 228-243.
54. Westermann, B. (2010). Mitochondrial fusion and fission in cell life and death. Nat. Rev. Mol. Cell Biol. 11, 872-884.
55. Wikstrom, J. D., Twig, G. and Shirihai, O. S. (2009). What can mitochondrial heterogeneity tell us about mitochondrial dynamics and autophagy? Int. J. Biochem. Cell Biol. 41, 1914-1927.
56. 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.
57. Yuan, H., Gerencser, A. A., Liot, G., Lipton, S. A., Ellisman, M., Perkins, G. A. and Bossy-Wetzel, E. (2007). Mitochondrial fission is an upstream and required event for bax foci formation in response to nitric oxide in cortical neurons. Cell Death Differ. 14, 462-471.
58. Zhao, J., Liu, T., Jin, S., Wang, X., Qu, M., Uhlén, P., Tomilin, N., Shupliakov, O., Lendahl, U. and Nistér, M. (2011). Human MIEF1 recruits Drp1 to mitochondrial outer membranes and promotes mitochondrial fusion rather than fission. EMBO J. 30, 2762-2778.
59. 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.
60. Zhu, J. H., Horbinski, C., Guo, F., Watkins, S., Uchiyama, Y. and Chu, C. T. (2007). Regulation of autophagy by extracellular signal-regulated protein kinases during 1-methyl-4-phenylpyridinium-induced cell death. Am. J. Pathol. 170, 75-86.