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Parkinson’s Disease
Volume 2012, Article ID 382175, 16 pages
http://dx.doi.org/10.1155/2012/382175
Review Article

The Emerging Role of Proteolysis in Mitochondrial Quality Control and the Etiology of Parkinson’s Disease

Biochemistry, University of Toronto, 1 King's College Circle, Toronto, ON, Canada M5S 1A8

Received 8 December 2011; Accepted 19 February 2012

Academic Editor: Catarina Resende de Oliveira

Copyright © 2012 Riya Shanbhag et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. T. Nakamura and S. A. Lipton, “Cell death: protein misfolding and neurodegenerative diseases,” Apoptosis, vol. 14, no. 4, pp. 455–468, 2009. View at Publisher · View at Google Scholar · View at Scopus
  2. D. M. Branco et al., “Cross-talk between mitochondria and proteasome in Parkinson's disease pathogenesis,” Frontiers in Aging Neuroscience, vol. 2, article 17, pp. 1–10, 2010. View at Publisher · View at Google Scholar
  3. M. Karbowski and A. Neutzner, “Neurodegeneration as a consequence of failed mitochondrial maintenance,” Acta Neuropathologica, vol. 123, no. 2, pp. 157–171, 2012. View at Publisher · View at Google Scholar
  4. E.M. Valente et al., “Molecular pathways in sporadic PD,” Parkinsonism & Related Disorders, vol. 18, supplement 1, pp. S71–S73, 2012. View at Google Scholar
  5. T. Tatsuta, “Protein quality control in mitochondria,” Journal of Biochemistry, vol. 146, no. 4, pp. 455–461, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. L. Devi and H. K. Anandatheerthavarada, “Mitochondrial trafficking of app and alpha synuclein: relevance to mitochondrial dysfunction in alzheimer's and parkinson's diseases,” Biochimica Et Biophysica Acta, vol. 1802, no. 1, pp. 11–19, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. L. Devi, B. M. Prabhu, D. F. Galati, N. G. Avadhani, and H. K. Anandatheerthavarada, “Accumulation of amyloid precursor protein in the mitochondrial import channels of human alzheimer's disease brain is associated with mitochondrial dysfunction,” Journal of Neuroscience, vol. 26, no. 35, pp. 9057–9068, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. U. Shirendeb, A. P. Reddy, M. Manczak et al., “Abnormal mitochondrial dynamics, mitochondrial loss and mutant huntingtin oligomers in huntington's disease: implications for selective neuronal damage,” Human Molecular Genetics, vol. 20, no. 7, Article ID ddr024, pp. 1438–1455, 2011. View at Publisher · View at Google Scholar · View at Scopus
  9. G. Twig, B. Hyde, and O. S. Shirihai, “Mitochondrial fusion, fission and autophagy as a quality control axis: the bioenergetic view,” Biochimica Et Biophysica Acta, vol. 1777, no. 9, pp. 1092–1097, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. Z. Makhosazane, S. Jonathan, and M. S. Willis, “All the little pieces: regulation of mitochondrial fusion and fission by ubiquitin and small ubiquitin-like modifier and their potential relevance in the heart,” Circulation Journal, vol. 75, no. 11, pp. 2513–2521, 2011. View at Publisher · View at Google Scholar
  11. J. M. Heo and J. Rutter, “Ubiquitin-dependent mitochondrial protein degradation,” International Journal of Biochemistry and Cell Biology, vol. 43, no. 10, pp. 1422–1426, 2011. View at Publisher · View at Google Scholar · View at Scopus
  12. M. Karbowski and R. J. Youle, “Regulating mitochondrial outer membrane proteins by ubiquitination and proteasomal degradation,” Current Opinion in Cell Biology, vol. 23, no. 4, pp. 476–482, 2011. View at Publisher · View at Google Scholar · View at Scopus
  13. N. Livnat-Levanon and M. H. Glickman, “Ubiquitin-proteasome system and mitochondria—reciprocity,” Biochimica Et Biophysica Acta, vol. 1809, no. 2, pp. 80–87, 2011. View at Publisher · View at Google Scholar · View at Scopus
  14. E. B. Taylor and J. Rutter, “Mitochondrial quality control by the ubiquitin-proteasome system,” Biochemical Society Transactions, vol. 39, no. 5, pp. 1509–1513, 2011. View at Publisher · View at Google Scholar
  15. T. Pan, S. Kondo, W. Le, and J. Jankovic, “The role of autophagy-lysosome pathway in neurodegeneration associated with parkinson's disease,” Brain, vol. 131, no. 8, pp. 1969–1978, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. D. C. Rubinsztein, G. Mariño, and G. Kroemer, “Autophagy and aging,” Cell, vol. 146, no. 5, pp. 682–695, 2011. View at Publisher · View at Google Scholar
  17. R. J. Youle and D. P. Narendra, “Mechanisms of mitophagy,” Nature Reviews Molecular Cell Biology, vol. 12, no. 1, pp. 9–14, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. I. Novak, “Mitophagy: a complex mechanism of mitochondrial removal,” Antioxid Redox Signal. In press. View at Publisher · View at Google Scholar
  19. A. S. Rambold and J. Lippincott-Schwartz, “Mechanisms of mitochondria and autophagy crosstalk,” Cell Cycle, vol. 10, no. 23, pp. 4032–4038, 2011. View at Publisher · View at Google Scholar
  20. M. Müller and A. S. Reichert, “Mitophagy, mitochondrial dynamics and the general stress response in yeast,” Biochemical Society Transactions, vol. 39, no. 5, pp. 1514–1519, 2011. View at Publisher · View at Google Scholar
  21. M. Mortensen, D. J. P. Ferguson, M. Edelmann et al., “Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 2, pp. 832–837, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. J. Peng, D. Schwartz, J. E. Elias et al., “A proteomics approach to understanding protein ubiquitination,” Nature Biotechnology, vol. 21, no. 8, pp. 921–926, 2003. View at Publisher · View at Google Scholar · View at Scopus
  23. H. B. Jeon, E. S. Choi, J. H. Yoon et al., “A proteomics approach to identify the ubiquitinated proteins in mouse heart,” Biochemical and Biophysical Research Communications, vol. 357, no. 3, pp. 731–736, 2007. View at Publisher · View at Google Scholar · View at Scopus
  24. C. Behrends and J. W. Harper, “Constructing and decoding unconventional ubiquitin chains,” Nature Structural and Molecular Biology, vol. 18, no. 5, pp. 520–528, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. Z. Zhaung and R. McCauley, “Ubiquitin is involved in the in vitro insertion of monoamine oxidase b into mitochondrial outer membranes,” Journal of Biological Chemistry, vol. 264, no. 25, pp. 14594–14596, 1989. View at Google Scholar · View at Scopus
  26. A. Cuconati, C. Mukherjee, D. Perez, and E. White, “Dna damage response and mcl-1 destruction initiate apoptosis in adenovirus-infected cells,” Genes and Development, vol. 17, no. 23, pp. 2922–2932, 2003. View at Publisher · View at Google Scholar · View at Scopus
  27. D. Nijhawan, M. Fang, E. Traer et al., “Elimination of mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation,” Genes and Development, vol. 17, no. 12, pp. 1475–1486, 2003. View at Publisher · View at Google Scholar · View at Scopus
  28. H. Wang, P. Song, L. Du et al., “Parkin ubiquitinates drp1 for proteasome-dependent degradation: implication of dysregulated mitochondrial dynamics in parkinson disease,” Journal of Biological Chemistry, vol. 286, no. 13, pp. 11649–11658, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. L. Glauser, S. Sonnay, K. Stafa, and D. J. Moore, “Parkin promotes the ubiquitination and degradation of the mitochondrial fusion factor mitofusin 1,” Journal of Neurochemistry, vol. 118, no. 4, pp. 636–645, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. A. Tanaka, M. M. Cleland, S. Xu et al., “Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by parkin,” Journal of Cell Biology, vol. 191, no. 7, pp. 1367–1380, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. D. H. Margineantu, C. B. Emerson, D. Diaz, and D. M. Hockenbery, “Hsp90 inhibition decreases mitochondrial protein turnover,” Plos one, vol. 2, no. 10, Article ID e1066, 2007. View at Publisher · View at Google Scholar · View at Scopus
  32. S. Radke, H. Chander, P. Schäfer et al., “Mitochondrial protein quality control by the proteasome involves ubiquitination and the protease omi,” Journal of Biological Chemistry, vol. 283, no. 19, pp. 12681–12685, 2008. View at Publisher · View at Google Scholar · View at Scopus
  33. V. Azzu and M. D. Brand, “Degradation of an intramitochondrial protein by the cytosolic proteasome,” Journal of Cell Science, vol. 123, no. 4, pp. 578–585, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. V. Azzu, S. A. Mookerjee, and M. D. Brand, “Rapid turnover of mitochondrial uncoupling protein 3,” Biochemical Journal, vol. 426, no. 1, pp. 13–17, 2010. View at Publisher · View at Google Scholar · View at Scopus
  35. S. Xu, G. Peng, Y. Wang, S. Fang, and M. Karbowsk, “The aaa-atpase p97 is essential for outer mitochondrial membrane protein turnover,” Molecular Biology of the Cell, vol. 22, no. 3, pp. 291–300, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. J. M. Heo, N. Livnat-Levanon, E. B. Taylor et al., “A stress-responsive system for mitochondrial protein degradation,” Molecular Cell, vol. 40, no. 3, pp. 465–480, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. W. Li, M. H. Bengtson, A. Ulbrich et al., “Genome-wide and functional annotation of human e3 ubiquitin ligases identifies mulan, a mitochondrial e3 that regulates the organelle's dynamics and signaling,” Plos one, vol. 3, no. 1, Article ID e1487, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. A. Neutzner, R. J. Youle, and M. Karbowski, “Outer mitochondrial membrane protein degradation by the proteasome,” Novartis Foundation Symposium, vol. 287, pp. 4–20, 2007. View at Google Scholar · View at Scopus
  39. R. Yonashiro, S. Ishido, S. Kyo et al., “A novel mitochondrial ubiquitin ligase plays a critical role in mitochondrial dynamics,” Embo Journal, vol. 25, no. 15, pp. 3618–3626, 2006. View at Publisher · View at Google Scholar · View at Scopus
  40. Q. Zhong, W. Gao, F. Du, and X. Wang, “Mule/arf-bp1, a bh3-only e3 ubiquitin ligase, catalyzes the polyubiquitination of mcl-1 and regulates apoptosis,” Cell, vol. 121, no. 7, pp. 1085–1095, 2005. View at Publisher · View at Google Scholar · View at Scopus
  41. E. J. Katz, M. Isasa, and B. Crosas, “A new map to understand deubiquitination,” Biochemical Society Transactions, vol. 38, no. 1, pp. 21–28, 2010. View at Publisher · View at Google Scholar · View at Scopus
  42. S. M. B. Nijman, M. P. A. Luna-Vargas, A. Velds et al., “A genomic and functional inventory of deubiquitinating enzymes,” Cell, vol. 123, no. 5, pp. 773–786, 2005. View at Publisher · View at Google Scholar · View at Scopus
  43. D. Komander, M. J. Clague, and S. Urbé, “Breaking the chains: structure and function of the deubiquitinases,” Nature Reviews Molecular Cell Biology, vol. 10, no. 8, pp. 550–563, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. F. E. Reyes-Turcu, K. H. Ventii, and K. D. Wilkinson, “Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes,” Annual Review of Biochemistry, vol. 78, pp. 363–397, 2009. View at Publisher · View at Google Scholar · View at Scopus
  45. M. J. Lee, B. H. Lee, J. Hanna, R. W. King, and D. Finley, “Trimming of ubiquitin chains by proteasome-associated deubiquitinating enzymes,” Molecular and Cellular Proteomics, vol. 10, no. 5, Article ID R110.003871, 2011. View at Publisher · View at Google Scholar · View at Scopus
  46. H. Li and X. Lin, “Positive and negative signaling components involved in tnfα-induced nf-κb activation,” Cytokine, vol. 41, no. 1, pp. 1–8, 2008. View at Publisher · View at Google Scholar · View at Scopus
  47. A. Kovalenko, C. Chable-Bessia, G. Cantarella, A. Israël, D. Wallach, and G. Courtois, “The tumour suppressor cyld negatively regulates nf-κb signalling by deubiquitination,” Nature, vol. 424, no. 6950, pp. 801–805, 2003. View at Publisher · View at Google Scholar · View at Scopus
  48. I. E. Wartz, K. M. O'Rourke, H. Zhou et al., “De-ubiquitination and ubiquitin ligase domains of a20 downregulate nf-κb signalling,” Nature, vol. 430, no. 7000, pp. 694–699, 2004. View at Publisher · View at Google Scholar · View at Scopus
  49. Z. M. Eletr and K. D. Wilkinson, “An emerging model for bap1's role in regulating cell cycle progression,” Cell Biochemistry and Biophysics, vol. 60, no. 1-2, pp. 3–11, 2011. View at Publisher · View at Google Scholar · View at Scopus
  50. F. Stegmeier, M. Rape, V. M. Draviam et al., “Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities,” Nature, vol. 446, no. 7138, pp. 876–881, 2007. View at Publisher · View at Google Scholar · View at Scopus
  51. J. Murai, K. Yang, D. Dejsuphong, K. Hirota, S. Takeda, and A. D. D'Andrea, “The usp1/uaf1 complex promotes double-strand break repair through homologous recombination,” Molecular and Cellular Biology, vol. 31, no. 12, pp. 2462–2469, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. N. Popov, S. Herold, M. Llamazares, C. Schülein, and M. Eilers, “Fbw7 and usp28 regulate myc protein stability in response to dna damage,” Cell Cycle, vol. 6, no. 19, pp. 2327–2331, 2007. View at Google Scholar · View at Scopus
  53. T. D. Wiltshire, C. A. Lovejoy, T. Wang, F. Xia, M. J. O'Connor, and D. Cortez, “Sensitivity to poly(adp-ribose) polymerase (parp) inhibition identifies ubiquitin-specific peptidase 11 (usp11) as a regulator of dna double-strand break repair,” Journal of Biological Chemistry, vol. 285, no. 19, pp. 14565–14571, 2010. View at Publisher · View at Google Scholar · View at Scopus
  54. S. Singhal, M. C. Taylor, and R. T. Baker, “Deubiquitylating enzymes and disease,” Bmc Biochemistry, vol. 9, supplement 1, article S3, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. M. Hu, P. Li, L. Song et al., “Structure and mechanisms of the proteasome-associated deubiquitinating enzyme usp14,” Embo Journal, vol. 24, no. 21, pp. 3747–3756, 2005. View at Publisher · View at Google Scholar · View at Scopus
  56. P. C. Chen, L. N. Qin, X. M. Li et al., “The proteasome-associated deubiquitinating enzyme usp14 is essential for the maintenance of synaptic ubiquitin levels and the development of neuromuscular junctions,” Journal of Neuroscience, vol. 29, no. 35, pp. 10909–10919, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. S. M. Wilson, B. Bhattacharyya, R. A. Rachel et al., “Synaptic defects in ataxia mice result from a mutation in usp14, encoding a ubiquitin-specific protease,” Nature Genetics, vol. 32, no. 3, pp. 420–425, 2002. View at Publisher · View at Google Scholar · View at Scopus
  58. Y. J. Machida, Y. Machida, A. A. Vashisht, J. A. Wohlschlegel, and A. Dutta, “The deubiquitinating enzyme bap1 regulates cell growth via interaction with hcf-1,” Journal of Biological Chemistry, vol. 284, no. 49, pp. 34179–34188, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. N. Nakamura and S. Hirose, “Regulation of mitochondrial morphology by usp30, a deubiquitinating enzyme present in the mitochondrial outer membrane,” Molecular Biology of the Cell, vol. 19, no. 5, pp. 1903–1911, 2008. View at Publisher · View at Google Scholar · View at Scopus
  60. V. Quesada, A. Díaz-Perales, A. Gutiérrez-Fernández, C. Garabaya, S. Cal, and C. López-Otín, “Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases,” Biochemical and Biophysical Research Communications, vol. 314, no. 1, pp. 54–62, 2004. View at Publisher · View at Google Scholar · View at Scopus
  61. A. Endo, N. Kitamura, and M. Komada, “Nucleophosmin/b23 regulates ubiquitin dynamics in nucleoli by recruiting deubiquitylating enzyme usp36,” Journal of Biological Chemistry, vol. 284, no. 41, pp. 27918–27923, 2009. View at Publisher · View at Google Scholar · View at Scopus
  62. M. S. Kim, S. Ramakrishna, K. H. Lim, J. H. Kim, and K. H. Baek, “Protein stability of mitochondrial superoxide dismutase sod2 is regulated by usp36,” Journal of Cellular Biochemistry, vol. 112, no. 2, pp. 498–508, 2011. View at Publisher · View at Google Scholar · View at Scopus
  63. M. Schwickart, X. Huang, J. R. Lill et al., “Deubiquitinase usp9x stabilizes mcl1 and promotes tumour cell survival,” Nature, vol. 463, no. 7277, pp. 103–107, 2010. View at Publisher · View at Google Scholar · View at Scopus
  64. Y. Huang, R. T. Baker, and J. A. Fischer-Vize, “Control of cell fate by a deubiquitinating enzyme encoded by the fat facets gene,” Science, vol. 270, no. 5243, pp. 1828–1831, 1995. View at Google Scholar · View at Scopus
  65. H. Chen, S. Polo, P. P. Di Fiore, and P. V. De Camilli, “Rapid ca2+-dependent decrease of protein ubiquitination at synapses,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 25, pp. 14908–14913, 2003. View at Publisher · View at Google Scholar · View at Scopus
  66. X. Zhang, J. Y. Zhou, M. H. Chin et al., “Region-specific protein abundance changes in the brain of mptp-lnduced parkinson's disease mouse model,” Journal of Proteome Research, vol. 9, no. 3, pp. 1496–1509, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. C. Pozzi, M. Valtorta, G. Tedeschi et al., “Study of subcellular localization and proteolysis of ataxin-3,” Neurobiology of Disease, vol. 30, no. 2, pp. 190–200, 2008. View at Publisher · View at Google Scholar · View at Scopus
  68. T. M. Durcan, M. Kontogiannea, T. Thorarinsdottir et al., “The machado-joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability,” Human Molecular Genetics, vol. 20, no. 1, pp. 141–154, 2011. View at Google Scholar · View at Scopus
  69. B. J. Winborn, S. M. Travis, S. V. Todi et al., “The deubiquitinating enzyme ataxin-3, a polyglutamine disease protein, edits lys63 linkages in mixed linkage ubiquitin chains,” Journal of Biological Chemistry, vol. 283, no. 39, pp. 26436–26443, 2008. View at Publisher · View at Google Scholar · View at Scopus
  70. J. M. Warrick, L. M. Morabito, J. Bilen et al., “Ataxin-3 suppresses polyglutamine neurodegeneration in drosophila by a ubiquitin-associated mechanism,” Molecular Cell, vol. 18, no. 1, pp. 37–48, 2005. View at Publisher · View at Google Scholar · View at Scopus
  71. Q. Wang, A. Li, and Y. Ye, “Regulation of retrotranslocation by p97-associated deubiquitinating enzyme ataxin-3,” Journal of Cell Biology, vol. 174, no. 7, pp. 963–971, 2006. View at Publisher · View at Google Scholar · View at Scopus
  72. X. Zhong and R. N. Pittman, “Ataxin-3 binds vcp/p97 and regulates retrotranslocation of erad substrates,” Human Molecular Genetics, vol. 15, no. 16, pp. 2409–2420, 2006. View at Publisher · View at Google Scholar · View at Scopus
  73. K. H. Oh, S. W. Yang, J. M. Park et al., “Control of aif-mediated cell death by antagonistic functions of chip ubiquitin e3 ligase and usp2 deubiquitinating enzyme,” Cell Death and Differentiation, vol. 18, no. 8, pp. 1326–1336, 2011. View at Publisher · View at Google Scholar · View at Scopus
  74. M. Metzig, D. Nickles, C. Falschlehner et al., “An rnai screen identifies usp2 as a factor required for tnf-α-induced nf-κb signaling,” International Journal of Cancer, vol. 129, no. 3, pp. 607–618, 2011. View at Publisher · View at Google Scholar · View at Scopus
  75. H. Y. Joo, L. Zhai, C. Yang et al., “Regulation of cell cycle progression and gene expression by h2a deubiquitination,” Nature, vol. 449, no. 7165, pp. 1068–1072, 2007. View at Publisher · View at Google Scholar · View at Scopus
  76. J. Liu, H. J. Chung, M. Vogt et al., “Jtv1 co-activates fbp to induce usp29 transcription and stabilize p53 in response to oxidative stress,” Embo Journal, vol. 30, no. 5, pp. 846–858, 2011. View at Publisher · View at Google Scholar · View at Scopus
  77. B. Aressy, D. Jullien, M. Cazales et al., “A screen for deubiquitinating enzymes involved in the g2/m checkpoint identifies usp50 as a regulator of hsp90-dependent wee1 stability,” Cell Cycle, vol. 9, no. 18, pp. 3815–3822, 2010. View at Publisher · View at Google Scholar · View at Scopus
  78. A. Zimprich, “Genetics of parkinson's disease and essential tremor,” Current Opinion in Neurology, vol. 24, no. 4, pp. 318–323, 2011. View at Publisher · View at Google Scholar · View at Scopus
  79. T. Kitada, S. Asakawa, N. Hattori et al., “Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism,” Nature, vol. 392, no. 6676, pp. 605–608, 1998. View at Publisher · View at Google Scholar · View at Scopus
  80. T. M. Durcan, M. Kontogiannea, N. Bedard, S. S. Wing, and E. A. Fon, “Ataxin-3 deubiquitination is coupled to parkin ubiquitination via E2 ubiquitin-conjugating enzyme,” Journal of Biological Chemistry, vol. 287, no. 1, pp. 531–541, 2012. View at Publisher · View at Google Scholar
  81. E. M. Valente, P. M. Abou-Sleiman, V. Caputo et al., “Hereditary early-onset parkinson's disease caused by mutations in pink1,” Science, vol. 304, no. 5674, pp. 1158–1160, 2004. View at Publisher · View at Google Scholar · View at Scopus
  82. S. Kawajiri, S. Saiki, S. Sato, and N. Hattori, “Genetic mutations and functions of pink1,” Trends in Pharmacological Sciences, vol. 32, no. 10, pp. 573–580, 2011. View at Publisher · View at Google Scholar · View at Scopus
  83. H. L. Wang, A. H. Chou, A. S. Wu et al., “Park6 pink1 mutants are defective in maintaining mitochondrial membrane potential and inhibiting ros formation of substantia nigra dopaminergic neurons,” Biochimica Et Biophysica Acta, vol. 1812, no. 6, pp. 674–684, 2011. View at Publisher · View at Google Scholar · View at Scopus
  84. B. Heeman, C. Van den Haute, S. A. Aelvoet et al., “Depletion of pink1 affects mitochondrial metabolism, calcium homeostasis and energy maintenance,” Journal of Cell Science, vol. 124, no. 7, pp. 1115–1125, 2011. View at Publisher · View at Google Scholar · View at Scopus
  85. R. Rohkamm, “Comment on the contribution by A. Krupp and K. G. Ravens: 'Foudroyant course of generalized cryptococcosis with no signs of immune compromise',” Internist, vol. 33, no. 2, p. 127, 1992. View at Google Scholar
  86. S. Geisler, K. M. Holmström, A. Treis et al., “The pink1/parkin-mediated mitophagy is compromised by pd-associated mutations,” Autophagy, vol. 6, no. 7, pp. 871–878, 2010. View at Publisher · View at Google Scholar · View at Scopus
  87. E. Deas, N. W. Wood, and H. Plun-Favreau, “Mitophagy and parkinson's disease: the pink1-parkin link,” Biochimica Et Biophysica Acta, vol. 1813, no. 4, pp. 623–633, 2011. View at Publisher · View at Google Scholar · View at Scopus
  88. S. Kawajiri, S. Saiki, S. Sato et al., “Pink1 is recruited to mitochondria with parkin and associates with lc3 in mitophagy,” Febs Letters, vol. 584, no. 6, pp. 1073–1079, 2010. View at Publisher · View at Google Scholar · View at Scopus
  89. V. A. Morais, P. Verstreken, A. Roethig et al., “Parkinson's disease mutations in pink1 result in decreased complex i activity and deficient synaptic function,” Embo Molecular Medicine, vol. 1, no. 2, pp. 99–111, 2009. View at Publisher · View at Google Scholar · View at Scopus
  90. L. Flinn, H. Mortiboys, K. Volkmann, R. W. Kster, P. W. Ingham, and O. Bandmann, “Complex i deficiency and dopaminergic neuronal cell loss in parkin-deficient zebrafish (Danio rerio),” Brain, vol. 132, no. 6, pp. 1613–1623, 2009. View at Publisher · View at Google Scholar · View at Scopus
  91. A. Wood-Kaczmar, S. Gandhi, Z. Yao et al., “Pink1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons,” Plos One, vol. 3, no. 6, Article ID e2455, 2008. View at Publisher · View at Google Scholar · View at Scopus
  92. A. H.V. Schapira, “Progress in neuroprotection in Parkinson's disease,” European Journal of Neurology, vol. 15, supplement 1, pp. 5–13, 2008. View at Publisher · View at Google Scholar
  93. D. Narendra, A. Tanaka, D. F. Suen, and R. J. Youle, “Parkin is recruited selectively to impaired mitochondria and promotes their autophagy,” Journal of Cell Biology, vol. 183, no. 5, pp. 795–803, 2008. View at Publisher · View at Google Scholar · View at Scopus
  94. D. P. Narendra, S. M. Jin, A. Tanaka et al., “Pink1 is selectively stabilized on impaired mitochondria to activate parkin,” Plos Biology, vol. 8, no. 1, Article ID e1000298, 2010. View at Publisher · View at Google Scholar · View at Scopus
  95. N. C. Chan, A. M. Salazar, A. H. Pham et al., “Broad activation of the ubiquitin-proteasome system by parkin is critical for mitophagy,” Human Molecular Genetics, vol. 20, no. 9, Article ID ddr048, pp. 1726–1737, 2011. View at Publisher · View at Google Scholar · View at Scopus
  96. D. P. Narendra, L. A. Kane, D. N. Hauser, I. M. Fearnley, and R. J. Youle, “P62/sqstm1 is required for parkin-induced mitochondrial clustering but not mitophagy; vdac1 is dispensable for both,” Autophagy, vol. 6, no. 8, pp. 1090–1106, 2010. View at Publisher · View at Google Scholar · View at Scopus
  97. M. E. Gegg and A. H. V. Schapira, “Pink1-parkin-dependent mitophagy involves ubiquitination of mitofusins 1 and 2: implications for parkinson disease pathogenesis,” Autophagy, vol. 7, no. 2, pp. 243–245, 2011. View at Publisher · View at Google Scholar · View at Scopus
  98. M. E. Gegg, J. M. Cooper, K. Y. Chau, M. Rojo, A. H. V. Schapira, and J. W. Taanman, “Mitofusin 1 and mitofusin 2 are ubiquitinated in a pink1/parkin-dependent manner upon induction of mitophagy,” Human Molecular Genetics, vol. 19, no. 24, Article ID ddq419, pp. 4861–4870, 2010. View at Publisher · View at Google Scholar · View at Scopus
  99. S. M. Fleming, P. O. Fernagut, and M. F. Chesselet, “Genetic mouse models of parkinsonism: strengths and limitations,” Neurorx, vol. 2, no. 3, pp. 495–503, 2005. View at Publisher · View at Google Scholar · View at Scopus
  100. A. J. Whitworth, J. R. Lee, V. M.-W. Ho, R. Flick, R. Chowdhury, and G. A. McQuibban, “Rhomboid-7 and HtrA2/Omi act in a common pathway with the Parkinson's disease factors Pink1 and Parkin,” DMM Disease Models and Mechanisms, vol. 1, no. 2-3, pp. 168–174, 2008. View at Publisher · View at Google Scholar
  101. P. Seibler, J. Graziotto, H. Jeong, F. Simunovic, C. Klein, and D. Krainc, “Mitochondrial parkin recruitment is impaired in neurons derived from mutant pink1 induced pluripotent stem cells,” Journal of Neuroscience, vol. 31, no. 16, pp. 5970–5976, 2011. View at Publisher · View at Google Scholar · View at Scopus
  102. C. Vives-Bauza and S. Przedborski, “Pink1 points parkin to mitochondria,” Autophagy, vol. 6, no. 5, pp. 674–675, 2010. View at Publisher · View at Google Scholar · View at Scopus
  103. N. Matsuda, S. Sato, K. Shiba et al., “Pink1 stabilized by mitochondrial depolarization recruits parkin to damaged mitochondria and activates latent parkin for mitophagy,” Journal of Cell Biology, vol. 189, no. 2, pp. 211–221, 2010. View at Publisher · View at Google Scholar · View at Scopus
  104. Y. Kim, J. Park, S. Kim et al., “PINK1 controls mitochondrial localization of Parkin through direct phosphorylation,” Biochemical and Biophysical Research Communications, vol. 377, no. 3, pp. 975–980, 2008. View at Publisher · View at Google Scholar
  105. D. P. Narendra and R. J. Youle, “Targeting mitochondrial dysfunction: role for pink1 and parkin in mitochondrial quality control,” Antioxidants and Redox Signaling, vol. 14, no. 10, pp. 1929–1938, 2011. View at Publisher · View at Google Scholar · View at Scopus
  106. V. A. Morais, P. Verstreken, A. Roethig et al., “Parkinson's disease mutations in pink1 result in decreased complex i activity and deficient synaptic function,” Embo Molecular Medicine, vol. 1, no. 2, pp. 99–111, 2009. View at Publisher · View at Google Scholar · View at Scopus
  107. M. E. Gegg, J. M. Cooper, A. H. V. Schapira, and J. W. Taanman, “Silencing of pink1 expression affects mitochondrial dna and oxidative phosphorylation in dopaminergic cells,” Plos one, vol. 4, no. 3, Article ID e4756, 2009. View at Publisher · View at Google Scholar · View at Scopus
  108. W. Liu, R. Acín-Peréz, K. D. Geghman, G. Manfredi, B. Lu, and C. Li, “Pink1 regulates the oxidative phosphorylation machinery via mitochondrial fission,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 31, pp. 12920–12924, 2011. View at Publisher · View at Google Scholar · View at Scopus
  109. W. Lin and U. J. Kang, “Characterization of pink1 processing, stability, and subcellular localization,” Journal of Neurochemistry, vol. 106, no. 1, pp. 464–474, 2008. View at Publisher · View at Google Scholar · View at Scopus
  110. A. Weihofen, B. Ostaszewski, Y. Minami, and D. J. Selkoe, “Pink1 parkinson mutations, the cdc37/hsp90 chaperones and parkin all influence the maturation or subcellular distribution of pink1,” Human Molecular Genetics, vol. 17, no. 4, pp. 602–616, 2008. View at Publisher · View at Google Scholar · View at Scopus
  111. G. Shi, J. R. Lee, D. A. Grimes et al., “Functional alteration of parl contributes to mitochondrial dysregulation in parkinson's disease,” Human Molecular Genetics, vol. 20, no. 10, Article ID ddr077, pp. 1966–1974, 2011. View at Publisher · View at Google Scholar · View at Scopus
  112. E. Deas, H. Plun-Favreau, S. Gandhi et al., “Pink1 cleavage at position a103 by the mitochondrial protease parl,” Human Molecular Genetics, vol. 20, no. 5, Article ID ddq526, pp. 867–879, 2011. View at Publisher · View at Google Scholar · View at Scopus
  113. C. Meissner, H. Lorenz, A. Weihofen, D. J. Selkoe, and M. K. Lemberg, “The mitochondrial intramembrane protease parl cleaves human pink1 to regulate pink1 trafficking,” Journal of Neurochemistry, vol. 117, no. 5, pp. 856–867, 2011. View at Publisher · View at Google Scholar · View at Scopus
  114. S. M. Jin, M. Lazarou, C. Wang, L. A. Kane, D. P. Narendra, and R. J. Youle, “Mitochondrial membrane potential regulates pink1 import and proteolytic destabilization by parl,” Journal of Cell Biology, vol. 191, no. 5, pp. 933–942, 2010. View at Publisher · View at Google Scholar · View at Scopus
  115. J. E. Curran, J. B. M. Jowett, L. J. Abraham et al., “Genetic variation in parl influences mitochondrial content,” Human Genetics, vol. 127, no. 2, pp. 183–190, 2010. View at Publisher · View at Google Scholar · View at Scopus
  116. P. Martinelli and E. I. Rugarli, “Emerging roles of mitochondrial proteases in neurodegeneration,” Biochimica Et Biophysica Acta, vol. 1797, no. 1, pp. 1–10, 2010. View at Publisher · View at Google Scholar
  117. A. Sík, B. J. Passer, E. V. Koonin, and L. Pellegrini, “Self-regulated cleavage of the mitochondrial intramembrane-cleaving protease parl yields pβ, a nuclear-targeted peptide,” Journal of Biological Chemistry, vol. 279, no. 15, pp. 15323–15329, 2004. View at Publisher · View at Google Scholar · View at Scopus
  118. D. V. Jeyaraju, L. Xu, M. C. Letellier et al., “Phosphorylation and cleavage of presenilin-associated rhomboid-like protein (parl) promotes changes in mitochondrial morphology,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 49, pp. 18562–18567, 2006. View at Publisher · View at Google Scholar · View at Scopus
  119. G. Twig and O. S. Shirihai, “The interplay between mitochondrial dynamics and mitophagy,” Antioxidants and Redox Signaling, vol. 14, no. 10, pp. 1939–1951, 2011. View at Publisher · View at Google Scholar · View at Scopus
  120. A. E. Civitarese, P. S. MacLean, S. Carling et al., “Regulation of skeletal muscle oxidative capacity and insulin signaling by the mitochondrial rhomboid protease parl,” Cell Metabolism, vol. 11, no. 5, pp. 412–426, 2010. View at Publisher · View at Google Scholar · View at Scopus
  121. D. V. Jeyaraju, H. M. McBride, R. B. Hill, and L. Pellegrini, “Structural and mechanistic basis of Parl activity and regulation,” Cell Death and Differentiation, vol. 18, no. 9, pp. 1531–1539, 2011. View at Publisher · View at Google Scholar
  122. M. Herlan, F. Vogel, C. Bornhövd, W. Neupert, and A. S. Reichert, “Processing of mgm1 by the rhomboid-type protease pcp1 is required for maintenance of mitochondrial morphology and of mitochondrial dna,” Journal of Biological Chemistry, vol. 278, no. 30, pp. 27781–27788, 2003. View at Publisher · View at Google Scholar · View at Scopus
  123. H. Sesaki, C. D. Dunn, M. Iijima et al., “Ups1p, a conserved intermembrane space protein, regulates mitochondrial shape and alternative topogenesis of mgm1p,” Journal of Cell Biology, vol. 173, no. 5, pp. 651–658, 2006. View at Publisher · View at Google Scholar · View at Scopus
  124. G. A. McQuibban, S. Saurya, and M. Freeman, “Mitochondrial membrane remodelling regulated by a conserved rhomboid protease,” Nature, vol. 423, no. 6939, pp. 537–541, 2003. View at Publisher · View at Google Scholar · View at Scopus
  125. T. E. Roche, J. C. Baker, X. Yan et al., “Distinct regulatory properties of pyruvate dehydrogenase kinase and phosphatase isoforms,” Progress in Nucleic Acid Research and Molecular Biology, vol. 70, pp. 33–75, 2001. View at Google Scholar · View at Scopus
  126. M. A. Joshi, N. H. Jeoung, M. Obayashi et al., “Impaired growth and neurological abnormalities in branched-chain α-keto acid dehydrogenase kinase-deficient mice,” Biochemical Journal, vol. 400, no. 1, pp. 153–162, 2006. View at Publisher · View at Google Scholar · View at Scopus
  127. C. W. Olanow and K. St.P. McNaught, “Ubiquitin-proteasome system and Parkinson's disease,” Movement Disorders, vol. 21, no. 11, pp. 1806–1823, 2006. View at Publisher · View at Google Scholar
  128. M. C. Bennett, J. F. Bishop, Y. Leng, P. B. Chock, T. N. Chase, and M. M. Mouradian, “Degradation of α-synuclein by proteasome,” Journal of Biological Chemistry, vol. 274, no. 48, pp. 33855–33858, 1999. View at Publisher · View at Google Scholar · View at Scopus
  129. H. J. Rideout, K. E. Larsen, D. Sulzer, and L. Stefanis, “Proteasomal inhibition leads to formation of ubiquitin/α-synuclein-immunoreactive inclusions in pc12 cells,” Journal of Neurochemistry, vol. 78, no. 4, pp. 899–908, 2001. View at Publisher · View at Google Scholar · View at Scopus
  130. K. S. P. McNaught, R. Belizaire, O. Isacson, P. Jenner, and C. W. Olanow, “Altered proteasomal function in sporadic parkinson's disease,” Experimental Neurology, vol. 179, no. 1, pp. 38–46, 2003. View at Publisher · View at Google Scholar · View at Scopus
  131. S. Oddo, “The ubiquitin-proteasome system in alzheimer's disease,” Journal of Cellular and Molecular Medicine, vol. 12, no. 2, pp. 363–373, 2008. View at Publisher · View at Google Scholar · View at Scopus
  132. B. M. Riederer, G. Leuba, A. Vernay, and I. M. Riederer, “The role of the ubiquitin proteasome system in alzheimer's disease,” Experimental Biology and Medicine, vol. 236, no. 3, pp. 268–276, 2011. View at Publisher · View at Google Scholar · View at Scopus
  133. C. L. Masters, G. Simms, and N. A. Weinman, “Amyloid plaque core protein in alzheimer disease and down syndrome,” Proceedings of the National Academy of Sciences of the United States of America, vol. 82, no. 12, pp. 4245–4249, 1985. View at Google Scholar · View at Scopus
  134. K. S. Kosik, C. L. Joachim, and D. J. Selkoe, “Microtubule-associated protein tau (τ) is a major antigenic component of paired helical filaments in alzheimer disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 83, no. 11, pp. 4044–4048, 1986. View at Google Scholar · View at Scopus
  135. M. L. Salon, L. Pasquini, M. Besio Moreno, J. M. Pasquini, and E. Soto, “Relationship between β-amyloid degradation and the 26s proteasome in neural cells,” Experimental Neurology, vol. 180, no. 2, pp. 131–143, 2003. View at Publisher · View at Google Scholar · View at Scopus
  136. S. Oh, H. S. Hong, E. Hwang et al., “Amyloid peptide attenuates the proteasome activity in neuronal cells,” Mechanisms of Ageing and Development, vol. 126, no. 12, pp. 1292–1299, 2005. View at Publisher · View at Google Scholar · View at Scopus
  137. B. Boland, A. Kumar, S. Lee et al., “Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer's disease,” Journal of Neuroscience, vol. 28, no. 27, pp. 6926–6937, 2008. View at Publisher · View at Google Scholar
  138. R. A. Nixon, J. Wegiel, A. Kumar et al., “Extensive involvement of autophagy in alzheimer disease: an immuno-electron microscopy study,” Journal of Neuropathology and Experimental Neurology, vol. 64, no. 2, pp. 113–122, 2005. View at Google Scholar · View at Scopus
  139. C. A. Wilson, D. D. Murphy, B. I. Giasson, B. Zhang, J. Q. Trojanowski, and V. M.-Y. Lee, “Degradative organelles containing mislocalized α- and β-synuclein proliferate in presenilin-1 null neurons,” Journal of Cell Biology, vol. 165, no. 3, pp. 335–346, 2004. View at Publisher · View at Google Scholar
  140. G. Esselens, V. Oorschot, V. Baert et al., “Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway,” Journal of Cell Biology, vol. 166, no. 7, pp. 1041–1054, 2004. View at Publisher · View at Google Scholar · View at Scopus
  141. D. H. Chui, H. Tanahashi, K. Ozawa et al., “Transgenic mice with alzheimer presenilin 1 mutations show accelerated neurodegeneration without amyloid plaque formation,” Nature Medicine, vol. 5, no. 5, pp. 560–564, 1999. View at Publisher · View at Google Scholar · View at Scopus
  142. Q. Guo, B. L. Sopher, K. Furukawa et al., “Alzheimer's presenilin mutation sensitizes neural cells to apoptosis induced by trophic factor withdrawal and amyloid β-peptide: involvement of calcium and oxyradicals,” Journal of Neuroscience, vol. 17, no. 11, pp. 4212–4222, 1997. View at Google Scholar
  143. J. H. Lee, W. H. Yu, A. Kumar et al., “Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by alzheimer-related ps1 mutations,” Cell, vol. 141, no. 7, pp. 1146–1158, 2010. View at Publisher · View at Google Scholar · View at Scopus
  144. H. Moller, L. Mellemkjaer, J. K. McLaughlin, and J. H. Olsen, “Occurrence of different cancers in patients with parkinson's disease,” British Medical Journal, vol. 310, no. 6993, pp. 1500–1501, 1995. View at Google Scholar · View at Scopus
  145. J. H. Olsen, S. Friis, and K. Frederiksen, “Malignant melanoma and other types of cancer preceding parkinson disease,” Epidemiology, vol. 17, no. 5, pp. 582–587, 2006. View at Publisher · View at Google Scholar · View at Scopus
  146. V. Gogvadze, S. Orrenius, and B. Zhivotovsky, “Mitochondria in cancer cells: what is so special about them?” Trends in Cell Biology, vol. 18, no. 4, pp. 165–173, 2008. View at Publisher · View at Google Scholar · View at Scopus
  147. H. Plun-Favreau, P. A. Lewis, J. Hardy, L. M. Martins, and N. W. Wood, “Cancer and neurodegeneration: between the devil and the deep blue sea,” Plos Genetics, vol. 6, no. 12, p. e1001257, 2010. View at Publisher · View at Google Scholar · View at Scopus
  148. M. J. Devine, H. Plun-Favreau, and N. W. Wood, “Parkinson's disease and cancer: two wars, one front,” Nature Reviews Cancer, vol. 11, no. 11, pp. 812–823, 2011. View at Publisher · View at Google Scholar