The LRRK2 inhibitor GSK2578215A induces protective autophagy in SH-SY5Y cells: Involvement of Drp-1-mediated mitochondrial fission and mitochondrial-derived ROS signaling

Cell Death and Disease

Volumn 5, Issue 8, 2014, Pages

  Saez Atienzar, S ^a,b,c   Bonet Ponce, L ^b   Blesa, J R ^b   Romero, F J ^b   Murphy, M P ^d   Jordan, J ^a   Galindo, M F ^c  

^a UNIVERSITY OF CASTILLA LA MANCHA   (Spain)

^b UNIVERSITY OF VALENCIA   (Spain)

^c HOSPITAL GENERAL UNIVERSITARIO DE ALBACETE   (Spain)

^d UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

10-(6'-UBIQUINONYL)DECYLTRIPHENYLPHOSPHONIUM BROMIDE; 4-HYDROXY-2-NONENAL; ALDEHYDE; AMINOPYRIDINE DERIVATIVE; BENZAMIDE DERIVATIVE; BENZODIAZEPINE DERIVATIVE; DNM1L PROTEIN, HUMAN; GSK2578215A; GUANOSINE TRIPHOSPHATASE; LEUCINE RICH REPEAT KINASE 2; LRRK2 PROTEIN, HUMAN; LRRK2-IN1; MICROTUBULE ASSOCIATED PROTEIN; MITOCHONDRIAL PROTEIN; ORGANOPHOSPHORUS COMPOUND; PROTEIN SERINE THREONINE KINASE; PYRIMIDINE DERIVATIVE; SMALL INTERFERING RNA; UBIQUINONE;

ANALOGS AND DERIVATIVES; ANTAGONISTS AND INHIBITORS; AUTOPHAGY; DRUG EFFECTS; GENETICS; HUMAN; METABOLISM; MITOCHONDRIAL DYNAMICS; MITOCHONDRION; OXIDATIVE STRESS; RNA INTERFERENCE; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ALDEHYDES; AMINOPYRIDINES; AUTOPHAGY; BENZAMIDES; BENZODIAZEPINONES; CELL LINE, TUMOR; GTP PHOSPHOHYDROLASES; HUMANS; LEUCINE-RICH REPEAT SERINE-THREONINE PROTEIN KINASE-2; MICROTUBULE-ASSOCIATED PROTEINS; MITOCHONDRIA; MITOCHONDRIAL DYNAMICS; MITOCHONDRIAL PROTEINS; ORGANOPHOSPHORUS COMPOUNDS; OXIDATIVE STRESS; PROTEIN-SERINE-THREONINE KINASES; PYRIMIDINES; RNA INTERFERENCE; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; UBIQUINONE;

EID: 84906850990     PISSN: None     EISSN: 20414889     Source Type: Journal    
DOI: 10.1038/cddis.2014.320     Document Type: Article

References (63)

1. Gilks WP, Abou-Sleiman PM, Gandhi S, Jain S, Singleton A, Lees AJ et al. A common LRRK2 mutation in idiopathic Parkinson's disease. Lancet 2005; 365: 415-416.
2. Lesage S, Janin S, Lohmann E, Leutenegger AL, Leclere L, Viallet F et al. LRRK2 exon 41 mutations in sporadic Parkinson disease in Europeans. Arch Neurol 2007; 64: 425-430.
3. Bardien S, Lesage S, Brice A, Carr J. Genetic characteristics of leucine-rich repeat kinase 2 (LRRK2) associated Parkinson's disease. Parkinsonism Relat Disord 2011; 17: 501-508.
4. Alegre-Abarrategui J, Christian H, Lufino MM, Mutihac R, Venda LL, Ansorge O et al. LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. Hum Mol Genet 2009; 18: 4022-4034.
5. Gandhi PN, Wang X, Zhu X, Chen SG, Wilson-Delfosse AL. The Roc domain of leucine-rich repeat kinase 2 is sufficient for interaction with microtubules. J Neurosci Res 2008; 86: 1711-1720.
6. Gillardon F. Leucine-rich repeat kinase 2 phosphorylates brain tubulin-beta isoforms and modulates microtubule stability-a point of convergence in parkinsonian neurodegeneration? J Neurochem 2009; 110: 1514-1522.
7. Valiron O, Caudron N, Job D. Microtubule dynamics. Cell Mol Life Sci 2001; 58: 2069-2084.
8. Guerreiro PS, Huang Y, Gysbers A, Cheng D, Gai WP, Outeiro TF et al. LRRK2 interactions with alpha-synuclein in Parkinson's disease brains and in cell models. J Mol Med (Berl) 2013; 91: 513-522.
9. Meixner A, Boldt K, Van Troys M, Askenazi M, Gloeckner CJ, Bauer M et al. A QUICK screen for Lrrk2 interaction partners - leucine-rich repeat kinase 2 is involved in actin cytoskeleton dynamics. Mol Cell Proteom 2011; 10: M110 001172.
10. West AB, Moore DJ, Biskup S, Bugayenko A, Smith WW, Ross CA et al. Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci USA 2005; 102: 16842-16847.
11. Greggio E, Jain S, Kingsbury A, Bandopadhyay R, Lewis P, Kaganovich A et al. Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. Neurobiol Dis 2006; 23: 329-341.
12. Smith WW, Pei Z, Jiang H, Dawson VL, Dawson TM, Ross CA. Kinase activity of mutant LRRK2 mediates neuronal toxicity. Nat Neurosci 2006; 9: 1231-1233.
13. Tong Y, Shen J. Alpha-synuclein and LRRK2: partners in crime. Neuron 2009; 64: 771-773.
14. Lin X, Parisiadou L, Gu XL, Wang L, Shim H, Sun L et al. Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson's-disease-related mutant alpha-synuclein. Neuron 2009; 64: 807-827.
15. Wszolek ZK, Pfeiffer RF, Tsuboi Y, Uitti RJ, McComb RD, Stoessl AJ et al. Autosomal dominant parkinsonism associated with variable synuclein and tau pathology. Neurology 2004; 62: 1619-1622.
16. Gomez-Lazaro M, Bonekamp NA, Galindo MF, Jordan J, Schrader M. 6-Hydroxydopamine (6-OHDA) induces Drp1-dependent mitochondrial fragmentation in SH-SY5Y cells. Free Radic Biol Med 2008; 44: 1960-1969.
17. Gomez-Lazaro M, Galindo MF, Concannon CG, Segura MF, Fernandez-Gomez FJ, Llecha N et al. 6-Hydroxydopamine activates the mitochondrial apoptosis pathway through p38 MAPK-mediated, p53-independent activation of Bax and PUMA. J Neurochem 2008; 104: 1599-1612.
18. Exner N, Lutz AK, Haass C, Winklhofer KF. Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences. EMBO J 2012; 31: 3038-3062.
19. Iaccarino C, Crosio C, Vitale C, Sanna G, Carri MT, Barone P. Apoptotic mechanisms in mutant LRRK2-mediated cell death. Hum Mol Genet 2007; 16: 1319-1326.
20. Youle RJ, van der Bliek AM. Mitochondrial fission, fusion, and stress. Science 2012; 337: 1062-1065.
21. Youle RJ, Karbowski M. Mitochondrial fission in apoptosis. Nat Rev Mol Cell Biol 2005; 6: 657-663.
22. Galindo MF, Solesio ME, Atienzar-Aroca S, Zamora MJ, Jordan Bueso J. Mitochondrial dynamics and mitophagy in the 6-hydroxydopamine preclinical model of Parkinson's disease. Parkinsons Dis 2012; 2012: 131058.
23. Solesio ME, Prime TA, Logan A, Murphy MP, Del Mar Arroyo-Jimenez M, Jordan J et al. The mitochondria-targeted anti-oxidant MitoQ reduces aspects of mitochondrial fission in the 6-OHDA cell model of Parkinson's disease. Biochim Biophys Acta 2013; 1832: 174-182.
24. Solesio ME, Saez-Atienzar S, Jordan J, Galindo MF. Characterization of mitophagy in the 6-hydoxydopamine Parkinson's disease model. Toxicol Sci 2012; 129: 411-420.
25. Schon EA, Przedborski S. Mitochondria: the next (neurode)generation. Neuron 2011; 70: 1033-1053.
26. Labrousse AM, Zappaterra MD, Rube DA, van der Bliek AMC. elegans dynamin-related protein DRP-1 controls severing of the mitochondrial outer membrane. Mol Cell 1999; 4: 815-826.
27. Legesse-Miller A, Massol RH, Kirchhausen T. Constriction and Dnm1p recruitment are distinct processes in mitochondrial fission. Mol Biol Cell 2003; 14: 1953-1963.
28. Stafa K, Tsika E, Moser R, Musso A, Glauser L, Jones A et al. Functional interaction of Parkinson's disease-associated LRRK2 with members of the dynamin GTPase superfamily. Hum Mol Genet 2013; 23: 2055-2077.
29. Sridhar S, Botbol Y, Macian F, Cuervo AM. Autophagy and disease: always two sides to a problem. J Pathol 2012; 226: 255-273.
30. Loos B, Engelbrecht AM, Lockshin RA, Klionsky DJ, Zakeri Z. The variability of autophagy and cell death susceptibility: Unanswered questions. Autophagy 2013; 9: 1270-1285.
31. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 2000; 19: 5720-5728.
32. Yamamoto H, Kakuta S, Watanabe TM, Kitamura A, Sekito T, Kondo-Kakuta C et al. Atg9 vesicles are an important membrane source during early steps of autophagosome formation. J Cell Biol 2012; 198: 219-233.
33. Orenstein SJ, Kuo SH, Tasset I, Arias E, Koga H, Fernandez-Carasa I et al. Interplay of LRRK2 with chaperone-mediated autophagy. Nat Neurosci 2013; 16: 394-406.
34. Gomez-Suaga P, Churchill GC, Patel S, Hilfiker S. A link between LRRK2, autophagy and NAADP-mediated endolysosomal calcium signalling. Biochem Soc Trans 2012; 40: 1140-1146.
35. Gomez-Suaga P, Hilfiker S. LRRK2 as a modulator of lysosomal calcium homeostasis with downstream effects on autophagy. Autophagy 2012; 8: 692-693.
36. Biskup S, Moore DJ, Celsi F, Higashi S, West AB, Andrabi SA et al. Localization of LRRK2 to membranous and vesicular structures in mammalian brain. Ann Neurol 2006; 60: 557-569.
37. Yoritaka A, Hattori N, Uchida K, Tanaka M, Stadtman ER, Mizuno Y. Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc Natl Acad Sci USA 1996; 93: 2696-2701.
38. Hattori N, Wanga M, Taka H, Fujimura T, Yoritaka A, Kubo S et al. Toxic effects of dopamine metabolism in Parkinson's disease. Parkinsonism Relat Disord 2009; 15(Suppl 1): S35-S38.
39. Kramer T, Lo Monte F, Goring S, Okala Amombo GM, Schmidt B. Small molecule kinase inhibitors for LRRK2 and their application to Parkinson's Disease Models. ACS Chem Neurosci 2012; 3: 151-160.
40. Reith AD, Bamborough P, Jandu K, Andreotti D, Mensah L, Dossang P et al. GSK2578215A; a potent and highly selective 2-arylmethyloxy-5-substitutent-N- arylbenzamide LRRK2 kinase inhibitor. Bioorg Med Chem Lett 2012; 22: 5625-5629.
41. Law BM, Spain VA, Leinster VH, Chia R, Beilina A, Cho HJ et al. A direct interaction between leucine-rich repeat kinase 2 and specific beta-tubulin isoforms regulates tubulin acetylation. J Biol Chem 2014; 289: 895-908.
42. Parisiadou L, Xie C, Cho HJ, Lin X, Gu XL, Long CX et al. Phosphorylation of ezrin/radixin/moesin proteins by LRRK2 promotes the rearrangement of actin cytoskeleton in neuronal morphogenesis. J Neurosci 2009; 29: 13971-13980.
43. Kimura S, Noda T, Yoshimori T. Dissection of the autophagosome maturation process by a novel reporter protein, tandem fluorescent-tagged LC3. Autophagy 2007; 3: 452-460.
44. Cassidy-Stone A, Chipuk JE, Ingerman E, Song C, Yoo C, Kuwana T et al. Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization. Dev Cell 2008; 14: 193-204.
45. Manzoni C, Mamais A, Dihanich S, Abeti R, Soutar MP, Plun-Favreau H et al. Inhibition of LRRK2 kinase activity stimulates macroautophagy. Biochim Biophys Acta 2013; 1833: 2900-2910.
46. Higashi S, Moore DJ, Yamamoto R, Minegishi M, Sato K, Togo T et al. Abnormal localization of leucine-rich repeat kinase 2 to the endosomal-lysosomal compartment in lewy body disease. J Neuropathol Exp Neurol 2009; 68: 994-1005.
47. Tong Y, Yamaguchi H, Giaime E, Boyle S, Kopan R, Kelleher RJ 3rd et al. Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of alpha-synuclein, and apoptotic cell death in aged mice. Proc Natl Acad Sci USA 2010; 107: 9879-9884.
48. Tong Y, Giaime E, Yamaguchi H, Ichimura T, Liu Y, Si H et al. Loss of leucine-rich repeat kinase 2 causes age-dependent bi-phasic alterations of the autophagy pathway. Mol Neurodegener 2012; 7: 2.
49. Skibinski G, Nakamura K, Cookson MR, Finkbeiner S. Mutant LRRK2 toxicity in neurons depends on LRRK2 levels and synuclein but not kinase activity or inclusion bodies. J Neurosci 2014; 34: 418-433.
50. Wang X, Yan MH, Fujioka H, Liu J, Wilson-Delfosse A, Chen SG et al. LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1. Hum Mol Genet 2012; 21: 1931-1944.
51. Ding WX, Li M, Chen X, Ni HM, Lin CW, Gao W et al. Autophagy reduces acute ethanol-induced hepatotoxicity and steatosis inmice. Gastroenterology 2010; 139: 1740-1752.
52. Nakamura T, Lipton SA. Redox modulation by S-nitrosylation contributes to protein misfolding, mitochondrial dynamics, and neuronal synaptic damage in neurodegenerative diseases. Cell Death Differ 2011; 18: 1478-1486.
53. Solesio ME, Saez-Atienzar S, Jordan J, Galindo MF. 3-Nitropropionic acid induces autophagy by forming mitochondrial permeability transition pores rather than activating the mitochondrial fission pathway. Br J Pharmacol 2013; 168: 63-75.
54. Cho DH, Nakamura T, Fang J, Cieplak P, Godzik A, Gu Z et al. S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury. Science 2009; 324: 102-105.
55. Cho B, Choi SY, Cho HM, Kim HJ, Sun W. Physiological and pathological significance of dynamin-related protein 1 (Drp1)-dependent mitochondrial fission in the nervous system. Exp Neurobiol 2013; 22: 149-157.
56. Haun F, Nakamura T, Shiu AD, Cho DH, Tsunemi T, Holland EA et al. S-nitrosylation of dynamin-related protein 1 mediates mutant huntingtin-induced mitochondrial fragmentation and neuronal injury in Huntington's disease. Antioxid Redox Signal 2013; 19: 1173-1184.
57. Su YC, Qi X. Inhibition of excessive mitochondrial fission reduced aberrant autophagy and neuronal damage caused by LRRK2 G2019S mutation. Hum Mol Genet 2013; 22: 4545-4561.
58. Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature 2008; 451: 1069-1075.
59. Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 2006; 441: 885-889.
60. Komatsu M, Waguri S, Chiba T, Murata S, Iwata J, Tanida I et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 2006; 441: 880-884.
61. Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell 2011; 147: 728-741.
62. Hattoria N, Wanga M, Taka H, Fujimura T, Yoritaka A, Kubo S et al. Toxic effects of dopamine metabolism in Parkinson's disease. Parkinsonism Relat Disord 2009; 15(Suppl 1): S35-S38.
63. Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 2012; 8: 445-544.