Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Miro (Mitochondrial Rho)

  • Seongsoo Lee
  • Kun-Sun Lee
  • Sungun Huh
  • Bingwei LuEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101740


Historical Background

The Ras superfamily family of small GTPases consists of GTP binding-dependent molecular switches with diverse cellular functions. Two isoforms of an “atypical” Rho GTPases, named mitochondrial Rho (Miro), are the first identified mitochondrial-associated Ras superfamily members (Fransson et al. 2003). Evolutionary conserved Miro GTPase has been identified in humans (Fransson et al. 2003), yeast (Frederick et al. 2004), Drosophila (Guo et al. 2005), as well as plant (Yamaoka and Leaver 2008).

Functional studies of Miro in various organisms have suggested critical roles of Miro in regulating mitochondrial morphology (Fransson et al. 2003), inheritance (Frederick et al. 2004), and mitochondrial calcium homeostasis (Lee et al. 2016). It is also a key regulator of cytoskeleton-mediated, long-range mitochondrial transport in...

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  1. Brickley K, Stephenson FA. Trafficking kinesin protein (TRAK)-mediated transport of mitochondria in axons of hippocampal neurons. J Biol Chem. 2011;286:18079–92.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Fransson A, Ruusala A, Aspenstrom P. Atypical Rho GTPases have roles in mitochondrial homeostasis and apoptosis. J Biol Chem. 2003;278:6495–502.CrossRefPubMedGoogle Scholar
  3. Frederick RL, McCaffery JM, Cunningham KW, Okamoto K, Shaw JM. Yeast Miro GTPase, Gem1p, regulates mitochondrial morphology via a novel pathway. J Cell Biol. 2004;167:87–98.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Glater EE, Megeath LJ, Stowers RS, Schwarz TL. Axonal transport of mitochondria requires milton to recruit kinesin heavy chain and is light chain independent. J Cell Biol. 2006;173:545–57.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Guo X, Macleod GT, Wellington A, Hu F, Panchumarthi S, Schoenfield M, Marin L, Charlton MP, Atwood HL, Zinsmaier KE. The GTPase dMiro is required for axonal transport of mitochondria to Drosophila synapses. Neuron. 2005;47:379–93.CrossRefPubMedGoogle Scholar
  6. Iijima-Ando K, Sekiya M, Maruko-Otake A, Ohtake Y, Suzuki E, Lu B, Iijima KM. Loss of axonal mitochondria promotes tau-mediated neurodegeneration and Alzheimer’s disease-related tau phosphorylation via PAR-1. PLoS Genet. 2012;8:e1002918.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Kanfer G, Courtheoux T, Peterka M, Meier S, Soste M, Melnik A, Reis K, Aspenstrom P, Peter M, Picotti P, et al. Mitotic redistribution of the mitochondrial network by Miro and Cenp-F. Nat Commun. 2015;6:8015.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998;392:605–8.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Klosowiak JL, Focia PJ, Chakravarthy S, Landahl EC, Freymann DM, Rice SE. Structural coupling of the EF hand and C-terminal GTPase domains in the mitochondrial protein Miro. EMBO Rep. 2013;14:968–74.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Kornmann B, Osman C, Walter P. The conserved GTPase Gem1 regulates endoplasmic reticulum-mitochondria connections. Proc Natl Acad Sci U S A. 2011;108:14151–6.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Lee KS, Lu B. The myriad roles of Miro in the nervous system: axonal transport of mitochondria and beyond. Front Cell Neurosci. 2014;8:330.PubMedPubMedCentralGoogle Scholar
  12. Lee S, Lee KS, Huh S, Liu S, Lee DY, Hong SH, Yu K, Lu B. Polo kinase phosphorylates Miro to control ER-mitochondria contact sites and mitochondrial Ca(2+) homeostasis in neural stem cell development. Dev Cell. 2016;37:174–89.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Liu S, Sawada T, Lee S, Yu W, Silverio G, Alapatt P, Millan I, Shen A, Saxton W, Kanao T, et al. Parkinson’s disease-associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondria. PLoS Genet. 2012;8:e1002537.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Rizzuto R, De Stefani D, Raffaello A, Mammucari C. Mitochondria as sensors and regulators of calcium signalling. Nat Rev Mol Cell Biol. 2012;13:566–78.CrossRefPubMedGoogle Scholar
  15. Rowland AA, Voeltz GK. Endoplasmic reticulum-mitochondria contacts: function of the junction. Nat Rev Mol Cell Biol. 2012;13:607–25.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Russo GJ, Louie K, Wellington A, Macleod GT, Hu F, Panchumarthi S, Zinsmaier KE. Drosophila Miro is required for both anterograde and retrograde axonal mitochondrial transport. J Neurosci. 2009;29:5443–55.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Schon EA, Area-Gomez E. Mitochondria-associated ER membranes in Alzheimer disease. Mol Cell Neurosci. 2013;55:26–36.CrossRefPubMedGoogle Scholar
  18. Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, et al. Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science. 2004;304:1158–60.CrossRefPubMedGoogle Scholar
  19. Wang X, Winter D, Ashrafi G, Schlehe J, Wong YL, Selkoe D, Rice S, Steen J, Lavoie MJ, Schwarz TL. PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell. 2011;147:893–906.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Yamaoka S, Leaver CJ. EMB2473/MIRO1, an Arabidopsis Miro GTPase, is required for embryogenesis and influences mitochondrial morphology in pollen. Plant Cell. 2008;20:589–601.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Seongsoo Lee
    • 1
  • Kun-Sun Lee
    • 2
  • Sungun Huh
    • 3
  • Bingwei Lu
    • 3
    Email author
  1. 1.Gwangju CenterKorea Basic Science InstituteGwangjuKorea
  2. 2.BioNanotechnology Research CenterKorea Research Institute of Biotechnology and BioscienceDaejeonKorea
  3. 3.Department of PathologyStanford University School of MedicineStanfordUSA