PINK1 and Parkin: emerging themes in mitochondrial homeostasis

Current Opinion in Cell Biology

Volumn 45, Issue , 2017, Pages 83-91

  McWilliams, Thomas G ^a   Muqit, Miratul MK ^a  

^a UNIVERSITY OF DUNDEE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

PARKIN; PEPTIDES AND PROTEINS; PTEN INDUCED PUTATIVE KINASE 1; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG; PROTEIN KINASE; UBIQUITIN PROTEIN LIGASE;

CELL DAMAGE; CYTOLOGY; ENZYME REGULATION; HOMEOSTASIS; HUMAN; IN VIVO STUDY; INTRACELLULAR SIGNALING; MITOCHONDRIAL HOMEOSTASIS; MITOCHONDRION; MITOPHAGY; PATHOLOGY; PRIORITY JOURNAL; REVIEW; ANIMAL; METABOLISM; PARKINSON DISEASE; PHOSPHORYLATION; PHYSIOLOGY; PROTEIN PROCESSING; SIGNAL TRANSDUCTION; UBIQUITINATION;

ANIMALS; HOMEOSTASIS; HUMANS; MITOCHONDRIA; MITOCHONDRIAL DEGRADATION; PARKINSON DISEASE; PHOSPHORYLATION; PROTEIN KINASES; PROTEIN PROCESSING, POST-TRANSLATIONAL; SIGNAL TRANSDUCTION; UBIQUITIN-PROTEIN LIGASES; UBIQUITINATION;

EID: 85018513908     PISSN: 09550674     EISSN: 18790410     Source Type: Journal    
DOI: 10.1016/j.ceb.2017.03.013     Document Type: Review

References (58)

1. 1 Rogov, V., Dotsch, V., Johansen, T., Kirkin, V., Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy. Mol. Cell 53 (2014), 167–178.
2. 2 Bras, J., Guerreiro, R., Hardy, J., SnapShot: genetics of Parkinson's disease. Cell, 160, 2015 570–570 e571.
3. 3 Wai, T., Saita, S., Nolte, H., Muller, S., Konig, T., Richter-Dennerlein, R., Sprenger, H.G., Madrenas, J., Muhlmeister, M., Brandt, U., et al. The membrane scaffold SLP2 anchors a proteolytic hub in mitochondria containing PARL and the i-AAA protease YME1L. EMBO Rep. 17 (2016), 1844–1856.
4. 4 Pickrell, A.M., Youle, R.J., The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease. Neuron 85 (2015), 257–273.
5. 5 Yamano, K., Matsuda, N., Tanaka, K., The ubiquitin signal and autophagy: an orchestrated dance leading to mitochondrial degradation. EMBO Rep. 17 (2016), 300–316.
6. 6 Thomas, R.E., Andrews, L.A., Burman, J.L., Lin, W.Y., Pallanck, L.J., PINK1-Parkin pathway activity is regulated by degradation of PINK1 in the mitochondrial matrix. PLoS Genet., 10, 2014, e1004279.
7. 7• Ordureau, A., Sarraf, S.A., Duda, D.M., Heo, J.M., Jedrychowski, M.P., Sviderskiy, V.O., Olszewski, J.L., Koerber, J.T., Xie, T., Beausoleil, S.A., et al. Quantitative proteomics reveal a feedforward mechanism for mitochondrial PARKIN translocation and ubiquitin chain synthesis. Mol. Cell 56 (2014), 360–375 By quantitative ubiquitin proteomics, this paper demonstrates the contribution of feed-forward and feed-back amplification cycles of Parkin activation by PINK1 and Phospho-ubiquitin following mitochondrial depolarisation.
8. 8 Chaugule, V.K., Burchell, L., Barber, K.R., Sidhu, A., Leslie, S.J., Shaw, G.S., Walden, H., Autoregulation of Parkin activity through its ubiquitin-like domain. EMBO J. 30 (2011), 2853–2867.
9. 9•• Kane, L.A., Lazarou, M., Fogel, A.I., Li, Y., Yamano, K., Sarraf, S.A., Banerjee, S., Youle, R.J., PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J. Cell Biol. 205 (2014), 143–153.
10. 10•• Kazlauskaite, A., Kondapalli, C., Gourlay, R., Campbell, D.G., Ritorto, M.S., Hofmann, K., Alessi, D.R., Knebel, A., Trost, M., Muqit, M.M., Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65. Biochem. J. 460 (2014), 127–139.
11. 11•• Koyano, F., Okatsu, K., Kosako, H., Tamura, Y., Go, E., Kimura, M., Kimura, Y., Tsuchiya, H., Yoshihara, H., Hirokawa, T., et al. Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature 510 (2014), 162–166 These collective contributions describe the phosphorylation of ubiquitin at Serine 65 by PINK1. Phospho-ubiquitin is essential for the full activation of Parkin E3 ligase activity and induction of mitophagy. These papers highlight a previously unrecognised interplay between the post-translational modifications of phosphorylation and ubiquitin.
12. 12 Wauer, T., Swatek, K.N., Wagstaff, J.L., Gladkova, C., Pruneda, J.N., Michel, M.A., Gersch, M., Johnson, C.M., Freund, S.M., Komander, D., Ubiquitin Ser65 phosphorylation affects ubiquitin structure, chain assembly and hydrolysis. EMBO J. 34 (2015), 307–325.
13. 13 Kazlauskaite, A., Martinez-Torres, R.J., Wilkie, S., Kumar, A., Peltier, J., Gonzalez, A., Johnson, C., Zhang, J., Hope, A.G., Peggie, M., et al. Binding to serine 65-phosphorylated ubiquitin primes Parkin for optimal PINK1-dependent phosphorylation and activation. EMBO Rep. 16 (2015), 939–954.
14. 14 Kumar, A., Aguirre, J.D., Condos, T.E., Martinez-Torres, R.J., Chaugule, V.K., Toth, R., Sundaramoorthy, R., Mercier, P., Knebel, A., Spratt, D.E., et al. Disruption of the autoinhibited state primes the E3 ligase parkin for activation and catalysis. EMBO J. 34 (2015), 2506–2521.
15. 15 Wauer, T., Simicek, M., Schubert, A., Komander, D., Mechanism of phospho-ubiquitin-induced PARKIN activation. Nature 524 (2015), 370–374.
16. 16 Sauve, V., Lilov, A., Seirafi, M., Vranas, M., Rasool, S., Kozlov, G., Sprules, T., Wang, J., Trempe, J.F., Gehring, K., A Ubl/ubiquitin switch in the activation of Parkin. EMBO J. 34 (2015), 2492–2505.
17. 17 Yamano, K., Queliconi, B.B., Koyano, F., Saeki, Y., Hirokawa, T., Tanaka, K., Matsuda, N., Site-specific interaction mapping of phosphorylated ubiquitin to uncover Parkin activation. J. Biol. Chem. 290 (2015), 25199–25211.
18. 18 Durcan, T.M., Fon, E.A., The three ‘P's of mitophagy: PARKIN, PINK1, and post-translational modifications. Genes Dev. 29 (2015), 989–999.
19. 19 Ordureau, A., Heo, J.M., Duda, D.M., Paulo, J.A., Olszewski, J.L., Yanishevski, D., Rinehart, J., Schulman, B.A., Harper, J.W., Defining roles of PARKIN and ubiquitin phosphorylation by PINK1 in mitochondrial quality control using a ubiquitin replacement strategy. Proc. Natl. Acad. Sci. U. S. A. 112 (2015), 6637–6642.
20. 20 Okatsu, K., Koyano, F., Kimura, M., Kosako, H., Saeki, Y., Tanaka, K., Matsuda, N., Phosphorylated ubiquitin chain is the genuine Parkin receptor. J. Cell Biol. 209 (2015), 111–128.
21. 21• Lazarou, M., Sliter, D.A., Kane, L.A., Sarraf, S.A., Wang, C., Burman, J.L., Sideris, D.P., Fogel, A.I., Youle, R.J., The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524 (2015), 309–314.
22. 22• Heo, J.M., Ordureau, A., Paulo, J.A., Rinehart, J., Harper, J.W., The PINK1-PARKIN mitochondrial ubiquitylation pathway drives a program of OPTN/NDP52 recruitment and TBK1 activation to promote mitophagy. Mol. Cell 60 (2015), 7–20 These papers describe the key autophagy adaptor proteins involved in the downstream steps of mitophagy. Lazarou et al., also provide evidence for PINK1-mediated Parkin-independent mitophagy.
23. 23 Richter, B., Sliter, D.A., Herhaus, L., Stolz, A., Wang, C., Beli, P., Zaffagnini, G., Wild, P., Martens, S., Wagner, S.A., et al. Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes selective autophagy of damaged mitochondria. Proc. Natl. Acad. Sci. U. S. A. 113 (2016), 4039–4044.
24. 24 Nguyen, T.N., Padman, B.S., Usher, J., Oorschot, V., Ramm, G., Lazarou, M., Atg8 family LC3/GABARAP proteins are crucial for autophagosome-lysosome fusion but not autophagosome formation during PINK1/Parkin mitophagy and starvation. J. Cell Biol. 215 (2016), 857–874.
25. 25 Tsuboyama, K., Koyama-Honda, I., Sakamaki, Y., Koike, M., Morishita, H., Mizushima, N., The ATG conjugation systems are important for degradation of the inner autophagosomal membrane. Science 354 (2016), 1036–1041.
26. 26 Rojansky, R., Cha, M.Y., Chan, D.C., Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1. eLife, 5, 2016.
27. 27 Yamano, K., Fogel, A.I., Wang, C., van der Bliek, A.M., Youle, R.J., Mitochondrial Rab GAPs govern autophagosome biogenesis during mitophagy. eLife, 3, 2014, e01612.
28. 28• Lai, Y.C., Kondapalli, C., Lehneck, R., Procter, J.B., Dill, B.D., Woodroof, H.I., Gourlay, R., Peggie, M., Macartney, T.J., Corti, O., et al. Phosphoproteomic screening identifies Rab GTPases as novel downstream targets of PINK1. EMBO J. 34 (2015), 2840–2861 Combining phosphoproteomic screening and biochemical analyses, this study implicates several Rab proteins including Rab8A as downstream targets of PINK1 following mitochondrial damage.
29. 29 Randow, F., Youle, R.J., Self and nonself: how autophagy targets mitochondria and bacteria. Cell Host Microbe 15 (2014), 403–411.
30. 30• Pickrell, A.M., Huang, C.H., Kennedy, S.R., Ordureau, A., Sideris, D.P., Hoekstra, J.G., Harper, J.W., Youle, R.J., Endogenous Parkin preserves dopaminergic substantia nigral neurons following mitochondrial DNA mutagenic stress. Neuron 87 (2015), 371–381 This important proof-of-concept study demonstrates that genetic ablation of Parkin results in age-dependent neurodegeneration under conditions of constitutive mitochondrial stress by crossing Parkin-null mice with the PolG mitochondrial mutator mouse model.
31. 31 Dave, K.D., De Silva, S., Sheth, N.P., Ramboz, S., Beck, M.J., Quang, C., Switzer, R.C. 3rd, Ahmad, S.O., Sunkin, S.M., Walker, D., et al. Phenotypic characterization of recessive gene knockout rat models of Parkinson's disease. Neurobiol. Dis. 70 (2014), 190–203.
32. 32 Villeneuve, L.M., Purnell, P.R., Boska, M.D., Fox, H.S., Early expression of Parkinson's disease-related mitochondrial abnormalities in PINK1 knockout rats. Mol. Neurobiol. 53 (2016), 171–186.
33. 33 Fiesel, F.C., Ando, M., Hudec, R., Hill, A.R., Castanedes-Casey, M., Caulfield, T.R., Moussaud-Lamodiere, E.L., Stankowski, J.N., Bauer, P.O., Lorenzo-Betancor, O., (Patho-)physiological relevance of PINK1-dependent ubiquitin phosphorylation. EMBO. Rep. 16 (2015), 1114–1130.
34. 34 Chung, S.Y., Kishinevsky, S., Mazzulli, J.R., Graziotto, J., Mrejeru, A., Mosharov, E.V., Puspita, L., Valiulahi, P., Sulzer, D., Milner, T.A., et al. Parkin and PINK1 patient iPSC-derived midbrain dopamine neurons exhibit mitochondrial dysfunction and alpha-synuclein accumulation. Stem Cell Rep. 7 (2016), 664–677.
35. 35 Khaminets, A., Behl, C., Dikic, I., Ubiquitin-dependent and independent signals in selective autophagy. Trends Cell Biol. 26 (2016), 6–16.
36. 36 Herhaus, L., Dikic, I., Expanding the ubiquitin code through post-translational modification. EMBO Rep. 16 (2015), 1071–1083.
37. 37 Swaney, D.L., Rodriguez-Mias, R.A., Villen, J., Phosphorylation of ubiquitin at Ser65 affects its polymerization, targets, and proteome-wide turnover. EMBO Rep. 16 (2015), 1131–1144.
38. 38 Palikaras, K., Lionaki, E., Tavernarakis, N., Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans. Nature 521 (2015), 525–528.
39. 39 Vincow, E.S., Merrihew, G., Thomas, R.E., Shulman, N.J., Beyer, R.P., MacCoss, M.J., Pallanck, L.J., The PINK1-Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), 6400–6405.
40. 40 McWilliams, T.G., Ganley, I.G., Life in lights: tracking mitochondrial delivery to lysosomes in vivo. Autophagy 12 (2016), 2506–2507.
41. 41•• McWilliams, T.G., Prescott, A.R., Allen, G.F., Tamjar, J., Munson, M.J., Thomson, C., Muqit, M.M., Ganley, I.G., mito-QC illuminates mitophagy and mitochondrial architecture in vivo. J. Cell Biol. 214 (2016), 333–345.
42. 42•• Sun, N., Yun, J., Liu, J., Malide, D., Liu, C., Rovira, I.I., Holmstrom, K.M., Fergusson, M.M., Yoo, Y.H., Combs, C.A., et al. Measuring in vivo mitophagy. Mol. Cell 60 (2015), 685–696 These two papers employ novel reporter mouse models to describe the unique basal nature of mammalian mitophagy for the first time in vivo. These technological advances herald powerful tools to uncover the physiological roles of mitophagy.
43. 43 Ashrafi, G., Schlehe, J.S., LaVoie, M.J., Schwarz, T.L., Mitophagy of damaged mitochondria occurs locally in distal neuronal axons and requires PINK1 and Parkin. J. Cell Biol. 206 (2014), 655–670.
44. 44• Davis, C.H., Kim, K.Y., Bushong, E.A., Mills, E.A., Boassa, D., Shih, T., Kinebuchi, M., Phan, S., Zhou, Y., Bihlmeyer, N.A., et al. Transcellular degradation of axonal mitochondria. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), 9633–9638 Classically, mitochondrial delivery to the lysosome has been studied in the context of intracellular degradation. This paper is the first to describe axonal trans-mitophagy in vivo and provokes a reassessment of how mitophagy proceeds in complex systems.
45. 45 Davis, C.H., Marsh-Armstrong, N., Discovery and implications of transcellular mitophagy. Autophagy 10 (2014), 2383–2384.
46. 46 Hayakawa, K., Esposito, E., Wang, X., Terasaki, Y., Liu, Y., Xing, C., Ji, X., Lo, E.H., Transfer of mitochondria from astrocytes to neurons after stroke. Nature 535 (2016), 551–555.
47. 47• McLelland, G.L., Soubannier, V., Chen, C.X., McBride, H.M., Fon, E.A., Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control. EMBO J. 33 (2014), 282–295 This study implicates PINK1-Parkin signalling in the regulation of mitochondrial-derived vesicles (MDVs) following mitochondrial damage. MDVs were noted to contain selective damaged mitochondrial cargos that are targeted to the lysosome for destruction.
48. 48 Sugiura, A., McLelland, G.L., Fon, E.A., McBride, H.M., A new pathway for mitochondrial quality control: mitochondrial-derived vesicles. EMBO J. 33 (2014), 2142–2156.
49. 49 McLelland, G.L., Lee, S.A., McBride, H.M., Fon, E.A., Syntaxin-17 delivers PINK1/parkin-dependent mitochondrial vesicles to the endolysosomal system. J. Cell Biol. 214 (2016), 275–291.
50. 50 Matheoud, D., Sugiura, A., Bellemare-Pelletier, A., Laplante, A., Rondeau, C., Chemali, M., Fazel, A., Bergeron, J.J., Trudeau, L.E., Burelle, Y., et al. Parkinson's disease-related proteins PINK1 and Parkin repress mitochondrial antigen presentation. Cell 166 (2016), 314–327.
51. 51 Roberts, R.F., Fon, E.A., Presenting mitochondrial antigens: PINK1, Parkin and MDVs steal the show. Cell Res. 26 (2016), 1180–1181.
52. 52 Murley, A., Nunnari, J., The emerging network of mitochondria-organelle contacts. Mol. Cell 61 (2016), 648–653.
53. 53 Sugiura, A., Mattie, S., Prudent, J., McBride, H.M., Newly born peroxisomes are a hybrid of mitochondrial and ER-derived pre-peroxisomes. Nature 542 (2017), 251–254.
54. 54 Pao, K.C., Stanley, M., Han, C., Lai, Y.C., Murphy, P., Balk, K., Wood, N.T., Corti, O., Corvol, J.C., Muqit, M.M., et al. Probes of ubiquitin E3 ligases enable systematic dissection of parkin activation. Nat. Chem. Biol. 12 (2016), 324–331.
55. 55 Matsuda, W., Furuta, T., Nakamura, K.C., Hioki, H., Fujiyama, F., Arai, R., Kaneko, T., Single nigrostriatal dopaminergic neurons form widely spread and highly dense axonal arborizations in the neostriatum. J. Neurosci. 29 (2009), 444–453.
56. 56 Bolam, J.P., Pissadaki, E.K., Living on the edge with too many mouths to feed: why dopamine neurons die. Mov. Disord. 27 (2012), 1478–1483.
57. 57 Crittenden, J.R., Tillberg, P.W., Riad, M.H., Shima, Y., Gerfen, C.R., Curry, J., Housman, D.E., Nelson, S.B., Boyden, E.S., Graybiel, A.M., Striosome-dendron bouquets highlight a unique striatonigral circuit targeting dopamine-containing neurons. Proc. Natl. Acad. Sci. U. S. A. 113 (2016), 11318–11323.
58. 58 Howe, M.W., Dombeck, D.A., Rapid signalling in distinct dopaminergic axons during locomotion and reward. Nature 535 (2016), 505–510.