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Induction of PINK1/Parkin-Mediated Mitophagy

Protocol
Part of the Methods in Molecular Biology book series

Abstract

PINK1/Parkin mitophagy is a key mechanism to contribute mitochondrial quality control, and the defects are thought to be a cause of those Parkinson’s disease onsets. Upon loss of mitochondrial membrane potential, PINK1 and Parkin are activated to promote the proteasomal degradation of mitochondrial outer membrane proteins and selective elimination of damaged mitochondria by autophagy. In this chapter, we describe the methods for induction of PINK1/Parkin-mediated mitophagy in tissue culture cell lines.

Keywords:

Mitochondrial membrane potential Parkin PINK1 

References

  1. 1.
    Narendra D, Walker JE, Youle R (2012) Mitochondrial quality control mediated by PINK1 and Parkin: links to Parkinsonism. Cold Spring Harb Perspect Biol 4(11). doi:10.1101/cshperspect.a011338
  2. 2.
    Pickrell AM, Youle RJ (2015) The roles of PINK1, Parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron 85(2):257–273. doi:10.1016/j.neuron.2014.12.007 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    van der Merwe C, Jalali Sefid Dashti Z, Christoffels A, Loos B, Bardien S (2015) Evidence for a common biological pathway linking three Parkinson’s disease-causing genes: Parkin, PINK1 and DJ-1. Eur J Neurosci 41(9):1113–1125. doi:10.1111/ejn.12872 CrossRefPubMedGoogle Scholar
  4. 4.
    Lazarou M, Narendra DP, Jin SM, Tekle E, Banerjee S, Youle RJ (2013) PINK1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial binding. J Cell Biol 200(2):163–172. doi:10.1083/jcb.201210111 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Jin SM, Lazarou M, Wang C, Kane LA, Narendra DP, Youle RJ (2010) Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J Cell Biol 191(5):933–942. doi:10.1083/jcb.201008084 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Lazarou M, Jin SM, Kane LA, Youle RJ (2012) Role of PINK1 binding to the TOM complex and alternate intracellular membranes in recruitment and activation of the E3 ligase Parkin. Dev Cell 22(2):320–333. doi:10.1016/j.devcel.2011.12.014 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier CA, Sou YS, Saiki S, Kawajiri S, Sato F, Kimura M, Komatsu M, Hattori N, Tanaka K (2010) PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol 189(2):211–221. doi:10.1083/jcb.200910140 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, Cookson MR, Youle RJ (2010) PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol 8(1):e1000298. doi:10.1371/journal.pbio.1000298 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Yoshii SR, Kishi C, Ishihara N, Mizushima N (2011) Parkin mediates proteasome-dependent protein degradation and rupture of the outer mitochondrial membrane. J Biol Chem 286(22):19630–19640. doi:10.1074/jbc.M110.209338 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Geisler S, Holmstrom KM, Skujat D, Fiesel FC, Rothfuss OC, Kahle PJ, Springer W (2010) PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol 12(2):119–131. doi:10.1038/ncb2012 CrossRefPubMedGoogle Scholar
  11. 11.
    Gegg ME, Cooper JM, Chau KY, Rojo M, Schapira AH, Taanman JW (2010) Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/Parkin-dependent manner upon induction of mitophagy. Hum Mol Genet 19(24):4861–4870. doi:10.1093/hmg/ddq419 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Rakovic A, Grunewald A, Seibler P, Ramirez A, Kock N, Orolicki S, Lohmann K, Klein C (2010) Effect of endogenous mutant and wild-type PINK1 on Parkin in fibroblasts from Parkinson disease patients. Hum Mol Genet 19(16):3124–3137. doi:10.1093/hmg/ddq215 CrossRefPubMedGoogle Scholar
  13. 13.
    Heo JM, Ordureau A, Paulo JA, Rinehart J, Harper JW (2015) The PINK1-PARKIN mitochondrial Ubiquitylation pathway drives a program of OPTN/NDP52 recruitment and TBK1 activation to promote mitophagy. Mol Cell 60(1):7–20. doi:10.1016/j.molcel.2015.08.016 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Lazarou M, Sliter DA, Kane LA, Sarraf SA, Wang C, Burman JL, Sideris DP, Fogel AI, Youle RJ (2015) The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524(7565):309–314. doi:10.1038/nature14893 CrossRefPubMedPubMedCentralADSGoogle Scholar
  15. 15.
    Yang JY, Yang WY (2011) Spatiotemporally controlled initiation of Parkin-mediated mitophagy within single cells. Autophagy 7(10):1230–1238. doi:10.4161/auto.7.10.16626 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of NeurologyJuntendo University Graduate School of MedicineTokyoJapan
  2. 2.Department of Neuroscience for Neurodegenerative DisordersJuntendo University Graduate School of MedicineTokyoJapan

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