Threonine 56 phosphorylation of Bcl-2 is required for LRRK2 G2019S-induced mitochondrial depolarization and autophagy

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volumn 1852, Issue 1, 2015, Pages 12-21

  Su, Yu Chin ^a   Guo, Xing ^a   Qi, Xin ^a  

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

Author keywords

Bcl 2; LRRK2 G2019S; Mitochondrial depolarization; Mitophagy; Phosphorylation

Indexed keywords

ALANINE; ASPARTIC ACID; CITRATE SYNTHASE; LEUCINE RICH REPEAT KINASE 2; OUTER MEMBRANE PROTEIN; PROTEIN BCL 2; THREONINE; THREONINE 56; UNCLASSIFIED DRUG; LRRK2 PROTEIN, HUMAN; PROTEIN SERINE THREONINE KINASE;

ADULT; AGED; ANIMAL CELL; ARTICLE; AUTOPHAGOSOME; BRAIN CELL; CARCINOMA CELL; CELL DAMAGE; CELL FRACTIONATION; CELL MEMBRANE DEPOLARIZATION; CONTROLLED STUDY; DOPAMINERGIC NERVE CELL; DOWN REGULATION; ENZYME ACTIVITY; ENZYME BINDING; FEMALE; FIBROBLAST; GENE MUTATION; HUMAN; HUMAN CELL; IN VITRO STUDY; LYSOSOME; MALE; MASS SPECTROMETRY; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRION; MITOPHAGY; NERVE DEGENERATION; NEURITE; NEUROBLASTOMA CELL; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; RAT; RNA INTERFERENCE; STABLE EXPRESSION; TRANSIENT EXPRESSION; AUTOPHAGY; BINDING SITE; CHEMISTRY; HELA CELL LINE; METABOLISM; PHOSPHORYLATION; PHYSIOLOGY;

AUTOPHAGY; BINDING SITES; HELA CELLS; HUMANS; MITOCHONDRIA; MITOCHONDRIAL DEGRADATION; PHOSPHORYLATION; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS C-BCL-2; THREONINE;

EID: 84912122968     PISSN: 09254439     EISSN: 1879260X     Source Type: Journal    
DOI: 10.1016/j.bbadis.2014.11.009     Document Type: Article

References (53)

1. Barbas N.R. Cognitive, affective, and psychiatric features of Parkinson's disease. Clin. Geriatr. Med. 2006, 22:773-796. (v-vi).
2. Fahn S. Description of Parkinson's disease as a clinical syndrome. Ann. N. Y. Acad. Sci. 2003, 991:1-14.
3. Deng H., Le W., Guo Y., Hunter C.B., Xie W., Jankovic J. Genetic and clinical identification of Parkinson's disease patients with LRRK2 G2019S mutation. Ann. Neurol. 2005, 57:933-934.
4. Gilks W.P., Abou-Sleiman P.M., Gandhi S., Jain S., Singleton A., Lees A.J., Shaw K., Bhatia K.P., Bonifati V., Quinn N.P., Lynch J., Healy D.G., Holton J.L., Revesz T., Wood N.W. A common LRRK2 mutation in idiopathic Parkinson's disease. Lancet 2005, 365:415-416.
5. Kachergus J., Mata I.F., Hulihan M., Taylor J.P., Lincoln S., Aasly J., Gibson J.M., Ross O.A., Lynch T., Wiley J., Payami H., Nutt J., Maraganore D.M., Czyzewski K., Styczynska M., Wszolek Z.K., Farrer M.J., Toft M. Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder across European populations. Am. J. Hum. Genet. 2005, 76:672-680.
6. Di Fonzo A., Rohe C.F., Ferreira J., Chien H.F., Vacca L., Stocchi F., Guedes L., Fabrizio E., Manfredi M., Vanacore N., Goldwurm S., Breedveld G., Sampaio C., Meco G., Barbosa E., Oostra B.A., Bonifati V. A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease. Lancet 2005, 365:412-415.
7. Paisan-Ruiz C., Lang A.E., Kawarai T., Sato C., Salehi-Rad S., Fisman G.K., Al-Khairallah T., St George-Hyslop P., Singleton A., Rogaeva E. LRRK2 gene in Parkinson disease: mutation analysis and case control association study. Neurology 2005, 65:696-700.
8. Zimprich A., Biskup S., Leitner P., Lichtner P., Farrer M., Lincoln S., Kachergus J., Hulihan M., Uitti R.J., Calne D.B., Stoessl A.J., Pfeiffer R.F., Patenge N., Carbajal I.C., Vieregge P., Asmus F., Muller-Myhsok B., Dickson D.W., Meitinger T., Strom T.M., Wszolek Z.K., Gasser T. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 2004, 44:601-607.
9. Paisan-Ruiz C., Jain S., Evans E.W., Gilks W.P., Simon J., van der Brug M., Lopez de Munain A., Aparicio S., Gil A.M., Khan N., Johnson J., Martinez J.R., Nicholl D., Carrera I.M., Pena A.S., de Silva R., Lees A., Marti-Masso J.F., Perez-Tur J., Wood N.W., Singleton A.B. Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 2004, 44:595-600.
10. West A.B., Moore D.J., Choi C., Andrabi S.A., Li X., Dikeman D., Biskup S., Zhang Z., Lim K.L., Dawson V.L., Dawson T.M. Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. Hum. Mol. Genet. 2007, 16:223-232.
11. West A.B., Moore D.J., Biskup S., Bugayenko A., Smith W.W., Ross C.A., Dawson V.L., Dawson T.M. Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:16842-16847.
12. Mortiboys H., Johansen K.K., Aasly J.O., Bandmann O. Mitochondrial impairment in patients with Parkinson disease with the G2019S mutation in LRRK2. Neurology 2010, 75:2017-2020.
13. Wang X., Yan M.H., Fujioka H., Liu J., Wilson-Delfosse A., Chen S.G., Perry G., Casadesus G., Zhu X. LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1. Hum. Mol. Genet. 2012, 21:1931-1944.
14. Bravo-San Pedro J.M., Niso-Santano M., Gomez-Sanchez R., Pizarro-Estrella E., Aiastui-Pujana A., Gorostidi A., Climent V., Lopez de Maturana R., Sanchez-Pernaute R., Lopez de Munain A., Fuentes J.M., Gonzalez-Polo R.A. The LRRK2 G2019S mutant exacerbates basal autophagy through activation of the MEK/ERK pathway. Cell. Mol. Life Sci. 2013, 70:121-136.
15. Tsika E., Moore D.J. Mechanisms of LRRK2-mediated neurodegeneration. Curr. Neurol. Neurosci. Rep. 2012, 12:251-260.
16. Bravo-San Pedro J.M., Niso-Santano M., Gomez-Sanchez R., Pizarro-Estrella E., Aiastui-Pujana A., Gorostidi A., Climent V., Lopez de Maturana R., Sanchez-Pernaute R., Lopez de Munain A., Fuentes J.M., Gonzalez-Polo R.A. The LRRK2 G2019S mutant exacerbates basal autophagy through activation of the MEK/ERK pathway. Cell. Mol. Life Sci. 2013, 70:121-136.
17. Menalled L., El-Khodor B.F., Patry M., Suarez-Farinas M., Orenstein S.J., Zahasky B., Leahy C., Wheeler V., Yang X.W., MacDonald M., Morton A.J., Bates G., Leeds J., Park L., Howland D., Signer E., Tobin A., Brunner D. Systematic behavioral evaluation of Huntington's disease transgenic and knock-in mouse models. Neurobiol. Dis. 2009, 35:319-336.
18. Ramonet D., Daher J.P., Lin B.M., Stafa K., Kim J., Banerjee R., Westerlund M., Pletnikova O., Glauser L., Yang L., Liu Y., Swing D.A., Beal M.F., Troncoso J.C., McCaffery J.M., Jenkins N.A., Copeland N.G., Galter D., Thomas B., Lee M.K., Dawson T.M., Dawson V.L., Moore D.J. Dopaminergic neuronal loss, reduced neurite complexity and autophagic abnormalities in transgenic mice expressing G2019S mutant LRRK2. PLoS One 2011, 6:e18568.
19. Katsumata M., Kamada S., Tsujimoto Y. Bcl-2 with anti-apoptotic activity. Tanpakushitsu Kakusan Koso 1995, 40:2062-2073.
20. Shimizu S., Narita M., Tsujimoto Y. Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature 1999, 399:483-487.
21. Korsmeyer S.J. BCL-2 gene family and the regulation of programmed cell death. Cancer Res. 1999, 59:1693s-1700s.
22. Reed J.C. Bcl-2 and the regulation of programmed cell death. J. Cell Biol. 1994, 124:1-6.
23. Kroemer G. The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nat. Med. 1997, 3:614-620.
24. Pattingre S., Tassa A., Qu X., Garuti R., Liang X.H., Mizushima N., Packer M., Schneider M.D., Levine B. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 2005, 122:927-939.
25. He C., Bassik M.C., Moresi V., Sun K., Wei Y., Zou Z., An Z., Loh J., Fisher J., Sun Q., Korsmeyer S., Packer M., May H.I., Hill J.A., Virgin H.W., Gilpin C., Xiao G., Bassel-Duby R., Scherer P.E., Levine B. Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature 2012, 481:511-515.
26. Greggio E., Jain S., Kingsbury A., Bandopadhyay R., Lewis P., Kaganovich A., van der Brug M.P., Beilina A., Blackinton J., Thomas K.J., Ahmad R., Miller D.W., Kesavapany S., Singleton A., Lees A., Harvey R.J., Harvey K., Cookson M.R. Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. Neurobiol. Dis. 2006, 23:329-341.
27. Wang N.S., Unkila M.T., Reineks E.Z., Distelhorst C.W. Transient expression of wild-type or mitochondrially targeted Bcl-2 induces apoptosis, whereas transient expression of endoplasmic reticulum-targeted Bcl-2 is protective against Bax-induced cell death. J. Biol. Chem. 2001, 276:44117-44128.
28. Qi X., Qvit N., Su Y.C., Mochly-Rosen D. A novel Drp1 inhibitor diminishes aberrant mitochondrial fission and neurotoxicity. J. Cell Sci. 2013, 126:789-802.
29. Watanabe Y., Tanaka M. p62/SQSTM1 in autophagic clearance of a non-ubiquitylated substrate. J. Cell Sci. 2011, 124:2692-2701.
30. Renna M., Schaffner C., Brown K., Shang S., Tamayo M.H., Hegyi K., Grimsey N.J., Cusens D., Coulter S., Cooper J., Bowden A.R., Newton S.M., Kampmann B., Helm J., Jones A., Haworth C.S., Basaraba R.J., DeGroote M.A., Ordway D.J., Rubinsztein D.C., Floto R.A. Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection. J. Clin. Invest. 2011, 121:3554-3563.
31. Niu J., Yu M., Wang C., Xu Z. Leucine-rich repeat kinase 2 disturbs mitochondrial dynamics via Dynamin-like protein. J. Neurochem. 2012, 122:650-658.
32. Wredenberg A., Wibom R., Wilhelmsson H., Graff C., Wiener H.H., Burden S.J., Oldfors A., Westerblad H., Larsson N.G. Increased mitochondrial mass in mitochondrial myopathy mice. Proc. Natl. Acad. Sci. U. S. A. 2002, 99:15066-15071.
33. Grunewald A., Voges L., Rakovic A., Kasten M., Vandebona H., Hemmelmann C., Lohmann K., Orolicki S., Ramirez A., Schapira A.H., Pramstaller P.P., Sue C.M., Klein C. Mutant Parkin impairs mitochondrial function and morphology in human fibroblasts. PLoS One 2010, 5:e12962.
34. Mizushima N., Yoshimori T., Levine B. Methods in mammalian autophagy research. Cell 2010, 140:313-326.
35. Bibb J.A., Yan Z., Svenningsson P., Snyder G.L., Pieribone V.A., Horiuchi A., Nairn A.C., Messer A., Greengard P. Severe deficiencies in dopamine signaling in presymptomatic Huntington's disease mice. Proc. Natl. Acad. Sci. U. S. A. 2000, 97:6809-6814.
36. Narendra D., Tanaka A., Suen D.F., Youle R.J. Parkin-induced mitophagy in the pathogenesis of Parkinson disease. Autophagy 2009, 5:706-708.
37. Geisler S., Holmstrom K.M., Skujat D., Fiesel F.C., Rothfuss O.C., Kahle P.J., Springer W. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat. Cell Biol. 2010, 12:119-131.
38. Blagosklonny M.V. Unwinding the loop of Bcl-2 phosphorylation. Leukemia 2001, 15:869-874.
39. Kabeya Y., Mizushima N., Ueno T., Yamamoto A., Kirisako T., Noda T., Kominami E., Ohsumi Y., Yoshimori T. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000, 19:5720-5728.
40. Durkacz B.W., Omidiji O., Gray D.A., Shall S. (ADP-ribose)n participates in DNA excision repair. Nature 1980, 283:593-596.
41. Fu J., Jin J., Cichewicz R.H., Hageman S.A., Ellis T.K., Xiang L., Peng Q., Jiang M., Arbez N., Hotaling K., Ross C.A., Duan W. trans-(-)-Epsilon-Viniferin increases mitochondrial sirtuin 3 (SIRT3), activates AMP-activated protein kinase (AMPK), and protects cells in models of Huntington Disease. J. Biol. Chem. 2012, 287:24460-24472.
42. Yin X.M., Oltvai Z.N., Veis-Novack D.J., Linette G.P., Korsmeyer S.J. Bcl-2 gene family and the regulation of programmed cell death. Cold Spring Harb. Symp. Quant. Biol. 1994, 59:387-393.
43. Cheng E.H., Kirsch D.G., Clem R.J., Ravi R., Kastan M.B., Bedi A., Ueno K., Hardwick J.M. Conversion of Bcl-2 to a Bax-like death effector by caspases. Science 1997, 278:1966-1968.
44. Blagosklonny M.V., Schulte T., Nguyen P., Trepel J., Neckers L.M. Taxol-induced apoptosis and phosphorylation of Bcl-2 protein involves c-Raf-1 and represents a novel c-Raf-1 signal transduction pathway. Cancer Res. 1996, 56:1851-1854.
45. De Chiara G., Marcocci M.E., Torcia M., Lucibello M., Rosini P., Bonini P., Higashimoto Y., Damonte G., Armirotti A., Amodei S., Palamara A.T., Russo T., Garaci E., Cozzolino F. Bcl-2 phosphorylation by p38 MAPK: identification of target sites and biologic consequences. J. Biol. Chem. 2006, 281:21353-21361.
46. Torcia M., De Chiara G., Nencioni L., Ammendola S., Labardi D., Lucibello M., Rosini P., Marlier L.N., Bonini P., Dello Sbarba P., Palamara A.T., Zambrano N., Russo T., Garaci E., Cozzolino F. Nerve growth factor inhibits apoptosis in memory B lymphocytes via inactivation of p38 MAPK, prevention of Bcl-2 phosphorylation, and cytochrome c release. J. Biol. Chem. 2001, 276:39027-39036.
47. Gomez-Suaga P., Churchill G.C., Patel S., Hilfiker S. A link between LRRK2, autophagy and NAADP-mediated endolysosomal calcium signalling. Biochem. Soc. Trans. 2012, 40:1140-1146.
48. Bravo-San Pedro J.M., Gomez-Sanchez R., Niso-Santano M., Pizarro-Estrella E., Aiastui-Pujana A., Gorostidi A., Climent V., Lopez de Maturana R., Sanchez-Pernaute R., Lopez de Munain A., Fuentes J.M., Gonzalez-Polo R.A. The MAPK1/3 pathway is essential for the deregulation of autophagy observed in G2019S LRRK2 mutant fibroblasts. Autophagy 2012, 8:1537-1539.
49. Narendra D., Tanaka A., Suen D.F., Youle R.J. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J. Cell Biol. 2008, 183:795-803.
50. Okatsu K., Saisho K., Shimanuki M., Nakada K., Shitara H., Sou Y.S., Kimura M., Sato S., Hattori N., Komatsu M., Tanaka K., Matsuda N. p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria. Genes Cells 2010, 15:887-900.
51. Narendra D., Kane L.A., Hauser D.N., Fearnley I.M., Youle R.J. p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both. Autophagy 2010, 6:1090-1106.
52. McDermott-Roe C., Ye J., Ahmed R., Sun X.M., Serafin A., Ware J., Bottolo L., Muckett P., Canas X., Zhang J., Rowe G.C., Buchan R., Lu H., Braithwaite A., Mancini M., Hauton D., Marti R., Garcia-Arumi E., Hubner N., Jacob H., Serikawa T., Zidek V., Papousek F., Kolar F., Cardona M., Ruiz-Meana M., Garcia-Dorado D., Comella J.X., Felkin L.E., Barton P.J., Arany Z., Pravenec M., Petretto E., Sanchis D., Cook S.A. Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function. Nature 2011, 478:114-118.
53. Khader A., Yang W.L., Kuncewitch M., Jacob A., Prince J.M., Asirvatham J.R., Nicastro J., Coppa G.F., Wang P. Sirtuin 1 activation stimulates mitochondrial biogenesis and attenuates renal injury after ischemia-reperfusion. Transplantation 2014, 98:148-156.