pp 1-6 | Cite as

Short Overview

Protocol
Part of the Methods in Molecular Biology book series

Abstract

Mitochondrial autophagy (mitophagy) is a mitochondrial quality control mechanism that selectively removes damaged mitochondria via autophagic degradation. Autophagic adaptor/receptor proteins contribute to the selective degradation of damaged mitochondria by autophagy. A part of them containing both ubiquitin binding domains and Atg8 interacting motif (AIM)/LC3 interacting region (LIR) motifs, which bind to the autophagy-related protein 8 (Atg8) family (LC3 and GABARAP family), lead ubiquitylated (damaged) mitochondria to selective removal. On the other hand, some specific outer mitochondrial membrane-anchored proteins containing AIM/LIR motif function as another type of autophagy adaptor/receptor proteins. Here I briefly summarize mechanisms of mitophagy and its related proteins.

Keywords

Atg8 interacting motif (AIM)/LC3 interacting region (LIR) Autophagy adaptor Mitophagy 

References

  1. 1.
    Bratic A, Larsson NG (2013) The role of mitochondria in aging. J Clin Invest 123(3):951–957. doi:10.1172/JCI64125 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Lezi E, Swerdlow RH (2012) Mitochondria in neurodegeneration. Adv Exp Med Biol 942:269–286. doi:10.1007/978-94-007-2869-1_12 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Pagano G, Talamanca AA, Castello G, Cordero MD, d’Ischia M, Gadaleta MN, Pallardo FV, Petrovic S, Tiano L, Zatterale A (2014) Oxidative stress and mitochondrial dysfunction across broad-ranging pathologies: toward mitochondria-targeted clinical strategies. Oxidative Med Cell Longev 2014:541230. doi:10.1155/2014/541230 CrossRefGoogle Scholar
  4. 4.
    Szendroedi J, Frossard M, Klein N, Bieglmayer C, Wagner O, Pacini G, Decker J, Nowotny P, Muller M, Roden M (2012) Lipid-induced insulin resistance is not mediated by impaired transcapillary transport of insulin and glucose in humans. Diabetes 61(12):3176–3180. doi:10.2337/db12-0108 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Wallace DC (2012) Mitochondria and cancer. Nat Rev Cancer 12(10):685–698. doi:10.1038/nrc3365 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Mizushima N, Komatsu M (2011) Autophagy: renovation of cells and tissues. Cell 147(4):728–741. doi:10.1016/j.cell.2011.10.026 CrossRefPubMedGoogle Scholar
  7. 7.
    Galluzzi L, Pietrocola F, Levine B, Kroemer G (2014) Metabolic control of autophagy. Cell 159(6):1263–1276. doi:10.1016/j.cell.2014.11.006 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Green DR, Levine B (2014) To be or not to be? How selective autophagy and cell death govern cell fate. Cell 157(1):65–75. doi:10.1016/j.cell.2014.02.049 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Randow F, Youle RJ (2014) Self and nonself: how autophagy targets mitochondria and bacteria. Cell Host Microbe 15(4):403–411. doi:10.1016/j.chom.2014.03.012 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Rogov V, Dotsch V, Johansen T, Kirkin V (2014) Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy. Mol Cell 53(2):167–178. doi:10.1016/j.molcel.2013.12.014 CrossRefPubMedGoogle Scholar
  11. 11.
    Stolz A, Ernst A, Dikic I (2014) Cargo recognition and trafficking in selective autophagy. Nat Cell Biol 16(6):495–501. doi:10.1038/ncb2979 CrossRefPubMedGoogle Scholar
  12. 12.
    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
  13. 13.
    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
  14. 14.
    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
  15. 15.
    Kane LA, Lazarou M, Fogel AI, Li Y, Yamano K, Sarraf SA, Banerjee S, Youle RJ (2014) PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J Cell Biol 205(2):143–153. doi:10.1083/jcb.201402104 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Kazlauskaite A, Kondapalli C, Gourlay R, Campbell DG, Ritorto MS, Hofmann K, Alessi DR, Knebel A, Trost M, Muqit MM (2014) Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65. Biochem J 460(1):127–139. doi:10.1042/BJ20140334 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Koyano F, Okatsu K, Kosako H, Tamura Y, Go E, Kimura M, Kimura Y, Tsuchiya H, Yoshihara H, Hirokawa T, Endo T, Fon EA, Trempe JF, Saeki Y, Tanaka K, Matsuda N (2014) Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature 510(7503):162–166. doi:10.1038/nature13392 ADSPubMedGoogle Scholar
  18. 18.
    Ordureau A, Sarraf SA, Duda DM, Heo JM, Jedrychowski MP, Sviderskiy VO, Olszewski JL, Koerber JT, Xie T, Beausoleil SA, Wells JA, Gygi SP, Schulman BA, Harper JW (2014) Quantitative proteomics reveal a feedforward mechanism for mitochondrial PARKIN translocation and ubiquitin chain synthesis. Mol Cell 56(3):360–375. doi:10.1016/j.molcel.2014.09.007 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    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
  20. 20.
    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
  21. 21.
    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
  22. 22.
    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 ADSCrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    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
  24. 24.
    Kanki T, Wang K, Cao Y, Baba M, Klionsky DJ (2009) Atg32 is a mitochondrial protein that confers selectivity during mitophagy. Dev Cell 17(1):98–109. doi:10.1016/j.devcel.2009.06.014 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Okamoto K, Kondo-Okamoto N, Ohsumi Y (2009) Mitochondria-anchored receptor Atg32 mediates degradation of mitochondria via selective autophagy. Dev Cell 17(1):87–97. doi:10.1016/j.devcel.2009.06.013 CrossRefPubMedGoogle Scholar
  26. 26.
    Hanna RA, Quinsay MN, Orogo AM, Giang K, Rikka S, Gustafsson AB (2012) Microtubule-associated protein 1 light chain 3 (LC3) interacts with Bnip3 protein to selectively remove endoplasmic reticulum and mitochondria via autophagy. J Biol Chem 287(23):19094–19104. doi:10.1074/jbc.M111.322933 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Zhu Y, Massen S, Terenzio M, Lang V, Chen-Lindner S, Eils R, Novak I, Dikic I, Hamacher-Brady A, Brady NR (2013) Modulation of serines 17 and 24 in the LC3-interacting region of Bnip3 determines pro-survival mitophagy versus apoptosis. J Biol Chem 288(2):1099–1113. doi:10.1074/jbc.M112.399345 CrossRefPubMedGoogle Scholar
  28. 28.
    Novak I, Kirkin V, McEwan DG, Zhang J, Wild P, Rozenknop A, Rogov V, Lohr F, Popovic D, Occhipinti A, Reichert AS, Terzic J, Dotsch V, Ney PA, Dikic I (2010) Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep 11(1):45–51. doi:10.1038/embor.2009.256 CrossRefPubMedGoogle Scholar
  29. 29.
    Murakawa T, Yamaguchi O, Hashimoto A, Hikoso S, Takeda T, Oka T, Yasui H, Ueda H, Akazawa Y, Nakayama H, Taneike M, Misaka T, Omiya S, Shah AM, Yamamoto A, Nishida K, Ohsumi Y, Okamoto K, Sakata Y, Otsu K (2015) Bcl-2-like protein 13 is a mammalian Atg32 homologue that mediates mitophagy and mitochondrial fragmentation. Nat Commun 6:7527. doi:10.1038/ncomms8527 ADSCrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Liu L, Feng D, Chen G, Chen M, Zheng Q, Song P, Ma Q, Zhu C, Wang R, Qi W, Huang L, Xue P, Li B, Wang X, Jin H, Wang J, Yang F, Liu P, Zhu Y, Sui S, Chen Q (2012) Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol 14(2):177–185. doi:10.1038/ncb2422 CrossRefPubMedGoogle Scholar
  31. 31.
    Schweers RL, Zhang J, Randall MS, Loyd MR, Li W, Dorsey FC, Kundu M, Opferman JT, Cleveland JL, Miller JL, Ney PA (2007) NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci U S A 104(49):19500–19505. doi:10.1073/pnas.0708818104 ADSCrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Sandoval H, Thiagarajan P, Dasgupta SK, Schumacher A, Prchal JT, Chen M, Wang J (2008) Essential role for Nix in autophagic maturation of erythroid cells. Nature 454(7201):232–235. doi:10.1038/nature07006 ADSCrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Li W, Zhang X, Zhuang H, Chen HG, Chen Y, Tian W, Wu W, Li Y, Wang S, Zhang L, Chen Y, Li L, Zhao B, Sui S, Hu Z, Feng D (2014) MicroRNA-137 is a novel hypoxia-responsive microRNA that inhibits mitophagy via regulation of two mitophagy receptors FUNDC1 and NIX. J Biol Chem 289(15):10691–10701. doi:10.1074/jbc.M113.537050 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Schiavi A, Maglioni S, Palikaras K, Shaik A, Strappazzon F, Brinkmann V, Torgovnick A, Castelein N, De Henau S, Braeckman BP, Cecconi F, Tavernarakis N, Ventura N (2015) Iron-starvation-induced mitophagy mediates lifespan extension upon mitochondrial stress in C. elegans. Curr Biol 25(14):1810–1822. doi:10.1016/j.cub.2015.05.059 CrossRefPubMedGoogle Scholar
  35. 35.
    Al Rawi S, Louvet-Vallee S, Djeddi A, Sachse M, Culetto E, Hajjar C, Boyd L, Legouis R, Galy V (2011) Postfertilization autophagy of sperm organelles prevents paternal mitochondrial DNA transmission. Science 334(6059):1144–1147. doi:10.1126/science.1211878 ADSCrossRefPubMedGoogle Scholar
  36. 36.
    Sato M, Sato K (2011) Degradation of paternal mitochondria by fertilization-triggered autophagy in C. elegans embryos. Science 334(6059):1141–1144. doi:10.1126/science.1210333 ADSCrossRefPubMedGoogle Scholar
  37. 37.
    Sato S, Furuya N (2017) Induction of PINK1/Parkin-mediated mitophagy. Methods Mol Biol. doi:10.1007/7651_2017_7 Google Scholar
  38. 38.
    Fujimaki M, Saiki S, Sasazawa Y, Ishikawa KI, Imamichi Y, Sumiyoshi K, Hattori N (2017) Immunocytochemical monitoring of PINK1/Parkin-mediated mitophagy in cultured cells. Methods Mol Biol. doi:10.1007/7651_2017_20 PubMedGoogle Scholar
  39. 39.
    Kishi-Itakura C, Buss F (2017) The use of correlative light-electron microscopy (CLEM) to study PINK1/Parkin-mediated mitophagy. Methods Mol Biol. doi:10.1007/7651_2017_8 PubMedGoogle Scholar
  40. 40.
    Inoshita T, Shiba-Fukushima K, Meng H, Hattori N, Imai Y (2017) Monitoring mitochondrial changes by alteration of the PINK1-Parkin signaling in Drosophila. Methods Mol Biol. doi:10.1007/7651_2017_9 PubMedGoogle Scholar
  41. 41.
    Ishikawa KI, Yamaguchi A, Okano H, Akamatsu W (2017) Assessment of mitophagy in iPS cell-derived neurons. Methods Mol Biol. doi:10.1007/7651_2017_10 CrossRefGoogle Scholar
  42. 42.
    Nagumo S, Okamoto K (2017) Investigation of yeast mitophagy with fluorescence microscopy and western blotting. Methods Mol Biol. doi:10.1007/7651_2017_11 PubMedGoogle Scholar
  43. 43.
    Yao Z, Liu X, Klionsky DJ (2017) MitoPho8Δ60 assay as a tool to quantitatively measure mitophagy activity. Methods Mol Biol. doi:10.1007/7651_2017_12 Google Scholar
  44. 44.
    Furukawa K, Kanki T (2017) Mitophagy in yeast: a screen of mitophagy-deficient mutants. Methods Mol Biol. doi:10.1007/7651_2017_13 PubMedGoogle Scholar
  45. 45.
    Šprung M, Dikic I, Novak I (2017) Flow cytometer monitoring of Bnip3- and Bnip3L/Nix-dependent mitophagy. Methods Mol Biol. doi:10.1007/7651_2017_14 PubMedGoogle Scholar
  46. 46.
    Li W, Chen H, Li S, Lin G, Feng D (2017) Exploring MicroRNAs on NIX-dependent mitophagy. Methods Mol Biol. doi:10.1007/7651_2017_15 Google Scholar
  47. 47.
    Arakawa S, Honda S, Torii S, Tsujioka M, Shimizu S (2017) Monitoring of Atg5-independent mitophagy. Methods Mol Biol. doi:10.1007/7651_2017_16 Google Scholar
  48. 48.
    Sato M, Sato K (2017) Monitoring of paternal mitochondrial degradation in Caenorhabditis elegans. Methods Mol Biol. doi:10.1007/7651_2017_17 Google Scholar
  49. 49.
    Yamashita SI, Kanki T (2017) Detection of hypoxia-induced and iron depletion-induced mitophagy in mammalian cells. Methods Mol Biol. doi:10.1007/7651_2017_19 Google Scholar
  50. 50.
    Charmpilas N, Kounakis K, Tavernarakis N (2017) Monitoring mitophagy during aging in Caenorhabditis elegans. Methods Mol Biol. doi:10.1007/7651_2017_18 PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

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

Personalised recommendations