PINK1-Parkin Pathway Activity Is Regulated by Degradation of PINK1 in the Mitochondrial Matrix

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Mitochondria are essential organelles that provide most of the cell's energy and perform many other critical functions. The gradual accumulation of defective mitochondria is thought to play a role in aging and in diseases of the nervous system, including Parkinson's disease. The selective elimination of defective mitochondria is therefore a vital task for the cell, and the protein PINK1 was recently identified as a critical player in this process. PINK1 accumulates on the surface of mitochondria after they are damaged, starting a process that leads ultimately to the elimination of defective mitochondria. Previous work indicated that PINK1 does not accumulate on healthy mitochondria because it is rapidly degraded. However, it was unclear exactly how and where this degradation occurred. Our work shows that Lon protease promotes the degradation of PINK1 in the mitochondrial matrix. This finding provides new insight into the mechanisms of mitochondrial quality control, and reveals a potential strategy for treating the many diseases associated with the accumulation of defective mitochondria.

Vyšlo v časopise: PINK1-Parkin Pathway Activity Is Regulated by Degradation of PINK1 in the Mitochondrial Matrix. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004279
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004279

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Zdroje

1. LeeHC, WeiYH (2012) Mitochondria and aging. Advances in Experimental Medicine and Biology 942: 311–327.

2. KarbowskiM, NeutznerA (2012) Neurodegeneration as a consequence of failed mitochondrial maintenance. Acta Neuropathologica 123: 157–171.

3. HoranMP, PichaudN, BallardJW (2012) Review: Quantifying Mitochondrial Dysfunction in Complex Diseases of Aging. The journals of gerontology Series A, Biological sciences and medical sciences 67: 1022–1035.

4. MariM, MoralesA, ColellA, Garcia-RuizC, KaplowitzN, et al. (2012) Mitochondrial glutathione: Features, regulation and role in disease. Biochimica et Biophysica Acta 1830 ((5)) 3317–28.

5. KoppenM, LangerT (2007) Protein degradation within mitochondria: versatile activities of AAA proteases and other peptidases. Critical Reviews in Biochemistry and Molecular Biology 42: 221–242.

6. TaylorEB, RutterJ (2011) Mitochondrial quality control by the ubiquitin-proteasome system. Biochemical Society Transactions 39: 1509–1513.

7. KitadaT, AsakawaS, HattoriN, MatsumineH, YamamuraY, et al. (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392: 605–608.

8. ValenteEM, Abou-SleimanPM, CaputoV, MuqitMM, HarveyK, et al. (2004) Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 304: 1158–1160.

9. NarendraD, TanakaA, SuenDF, YouleRJ (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. The Journal of Cell Biology 183: 795–803.

10. NarendraDP, JinSM, TanakaA, SuenDF, GautierCA, et al. (2010) PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS biology 8: e1000298.

11. Vives-BauzaC, ZhouC, HuangY, CuiM, de VriesRL, et al. (2010) PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci U S A 107: 378–383.

12. GreeneAW, GrenierK, AguiletaMA, MuiseS, FarazifardR, et al. (2012) Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment. EMBO Rep 13: 378–385.

13. WhitworthAJ, LeeJR, HoVM, FlickR, ChowdhuryR, et al. (2008) Rhomboid-7 and HtrA2/Omi act in a common pathway with the Parkinson's disease factors Pink1 and Parkin. Disease models & mechanisms 1: 168–174 discussion 173.

14. JinSM, LazarouM, WangC, KaneLA, NarendraDP, et al. (2010) Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J Cell Biol 191: 933–942.

15. SchneiderH, ArretzM, WachterE, NeupertW (1990) Matrix processing peptidase of mitochondria. Structure-function relationships. The Journal of Biological Chemistry 265: 9881–9887.

16. DeasE, Plun-FavreauH, GandhiS, DesmondH, KjaerS, et al. (2011) PINK1 cleavage at position A103 by the mitochondrial protease PARL. Human molecular genetics 20: 867–879.

17. LinW, KangUJ (2008) Characterization of PINK1 processing, stability, and subcellular localization. Journal of Neurochemistry 106 ((1)) 464–74.

18. TakatoriS, ItoG, IwatsuboT (2008) Cytoplasmic localization and proteasomal degradation of N-terminally cleaved form of PINK1. Neurosci Lett 430: 13–17.

19. WeihofenA, OstaszewskiB, MinamiY, SelkoeDJ (2008) Pink1 Parkinson mutations, the Cdc37/Hsp90 chaperones and Parkin all influence the maturation or subcellular distribution of Pink1. Human Molecular Genetics 17: 602–616.

20. ClarkIE, DodsonMW, JiangC, CaoJH, HuhJR, et al. (2006) Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441: 1162–1166.

21. MajorT, von JanowskyB, RuppertT, MogkA, VoosW (2006) Proteomic analysis of mitochondrial protein turnover: identification of novel substrate proteins of the matrix protease pim1. Mol Cell Biol 26: 762–776.

22. SuzukiCK, SudaK, WangN, SchatzG (1994) Requirement for the yeast gene LON in intramitochondrial proteolysis and maintenance of respiration. Science 264: 273–276.

23. LuB, LeeJ, NieX, LiM, MorozovYI, et al. (2013) Phosphorylation of human TFAM in mitochondria impairs DNA binding and promotes degradation by the AAA+ Lon protease. Mol Cell 49: 121–132.

24. LuB, YadavS, ShahPG, LiuT, TianB, et al. (2007) Roles for the human ATP-dependent Lon protease in mitochondrial DNA maintenance. J Biol Chem 282: 17363–17374.

25. MatsushimaY, GotoY, KaguniLS (2010) Mitochondrial Lon protease regulates mitochondrial DNA copy number and transcription by selective degradation of mitochondrial transcription factor A (TFAM). Proc Natl Acad Sci U S A 107: 18410–18415.

26. NargundAM, PellegrinoMW, FioreseCJ, BakerBM, HaynesCM (2012) Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation. Science 337: 587–590.

27. JinSM, YouleRJ (2013) The accumulation of misfolded proteins in the mitochondrial matrix is sensed by PINK1 to induce PARK2/Parkin-mediated mitophagy of polarized mitochondria. Autophagy 9: 1750–1757.

28. BurmanJL, YuS, PooleAC, DecalRB, PallanckL (2012) Analysis of neural subtypes reveals selective mitochondrial dysfunction in dopaminergic neurons from parkin mutants. Proceedings of the National Academy of Sciences of the United States of America 109: 10438–10443.

29. FrederickRL, McCafferyJM, CunninghamKW, OkamotoK, ShawJM (2004) Yeast Miro GTPase, Gem1p, regulates mitochondrial morphology via a novel pathway. J Cell Biol 167: 87–98.

30. LenaersG, ReynierP, ElachouriG, SoukkariehC, OlichonA, et al. (2009) OPA1 functions in mitochondria and dysfunctions in optic nerve. Int J Biochem Cell Biol 41: 1866–1874.

31. Heath-EngelHM, ShoreGC (2006) Mitochondrial membrane dynamics, cristae remodelling and apoptosis. Biochim Biophys Acta 1763: 549–560.

32. PooleAC, ThomasRE, AndrewsLA, McBrideHM, WhitworthAJ, et al. (2008) The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci U S A 105: 1638–1643.

33. GreeneJC, WhitworthAJ, KuoI, AndrewsLA, FeanyMB, et al. (2003) Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci U S A 100: 4078–4083.

34. ParkJ, LeeSB, LeeS, KimY, SongS, et al. (2006) Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature 441: 1157–1161.

35. VenkateshS, LeeJ, SinghK, LeeI, SuzukiCK (2012) Multitasking in the mitochondrion by the ATP-dependent Lon protease. Biochim Biophys Acta 1823: 56–66.

36. ShiG, LeeJR, GrimesDA, RacachoL, YeD, et al. (2011) Functional alteration of PARL contributes to mitochondrial dysregulation in Parkinson's disease. Human molecular genetics 20: 1966–1974.

37. GranotZ, KobilerO, Melamed-BookN, EimerlS, BahatA, et al. (2007) Turnover of mitochondrial steroidogenic acute regulatory (StAR) protein by Lon protease: the unexpected effect of proteasome inhibitors. Mol Endocrinol 21: 2164–2177.

38. GandhiS, MuqitMM, StanyerL, HealyDG, Abou-SleimanPM, et al. (2006) PINK1 protein in normal human brain and Parkinson's disease. Brain : a journal of neurology 129: 1720–1731.

39. PridgeonJW, OlzmannJA, ChinLS, LiL (2007) PINK1 Protects against Oxidative Stress by Phosphorylating Mitochondrial Chaperone TRAP1. PLoS Biology 5: e172.

40. BeckerD, RichterJ, TocilescuMA, PrzedborskiS, VoosW (2012) Pink1 kinase and its membrane potential (Deltapsi)-dependent cleavage product both localize to outer mitochondrial membrane by unique targeting mode. The Journal of Biological Chemistry 287: 22969–22987.

41. MoraisVA, HaddadD, CraessaertsK, De BockPJ, SwertsJ, et al. (2014) PINK1 Loss of Function Mutations Affect Mitochondrial Complex I Activity via NdufA10 Ubiquinone Uncoupling. Science 344: 203–207.

42. VincowES, MerrihewG, ThomasRE, ShulmanNJ, BeyerRP, et al. (2013) The PINK1-Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo. Proceedings of the National Academy of Sciences of the United States of America 110: 6400–6405.

43. McLellandGL, SoubannierV, ChenCX, McBrideHM, FonEA (2014) Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control. EMBO J 33: 282–295.

44. RussoGJ, LouieK, WellingtonA, MacleodGT, HuF, et al. (2009) Drosophila Miro is required for both anterograde and retrograde axonal mitochondrial transport. The Journal of neuroscience : the official journal of the Society for Neuroscience 29: 5443–5455.

45. SchusterCM, DavisGW, FetterRD, GoodmanCS (1996) Genetic dissection of structural and functional components of synaptic plasticity. I. Fasciclin II controls synaptic stabilization and growth. Neuron 17: 641–654.

46. RanganayakuluG, SchulzRA, OlsonEN (1996) Wingless signaling induces nautilus expression in the ventral mesoderm of the Drosophila embryo. Developmental Biology 176: 143–148.

47. HuY, SopkoR, FoosM, KelleyC, FlockhartI, et al. (2013) FlyPrimerBank: an online database for Drosophila melanogaster gene expression analysis and knockdown evaluation of RNAi reagents. G3 (Bethesda) 3: 1607–1616.

48. LingD, SalvaterraPM (2011) Robust RT-qPCR data normalization: validation and selection of internal reference genes during post-experimental data analysis. PLoS One 6: e17762.

49. ItsaraLS, KennedySR, FoxEJ, YuS, HewittJJ, et al. (2014) Oxidative stress is not a major contributor to somatic mitochondrial DNA mutations. PLoS genetics 10: e1003974.

50. ZivianiE, TaoRN, WhitworthAJ (2010) Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc Natl Acad Sci U S A 107: 5018–5023.

51. SchindelinJ, Arganda-CarrerasI, FriseE, KaynigV, LongairM, et al. (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9: 676–682.