Skip to main content
SpringerLink
Log in
Book cover

Pharmacology of Mitochondria pp 457–472Cite as

MITO-Porter for Mitochondrial Delivery and Mitochondrial Functional Analysis

  • Chapter
  • First Online:

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 240))

Abstract

Mitochondria are attractive organelles that have the potential to contribute greatly to medical therapy, the maintenance of beauty and health, and the development of the life sciences. Therefore, it would be expected that the further development of mitochondrial drug delivery systems (DDSs) would exert a significant impact on the medical and life sciences. To achieve such an innovative objective, it will be necessary to deliver various cargoes to mitochondria in living cells. However, only a limited number of approaches are available for accomplishing this. We recently proposed a new concept for mitochondrial delivery, a MITO-Porter, a liposome-based carrier that introduces macromolecular cargoes into mitochondria via membrane fusion. To date, we have demonstrated the utility of mitochondrial therapeutic strategy by MITO-Porter using animal models of diseases. We also showed that the mitochondrial delivery of antisense oligo-RNA by the MITO-Porter results in mitochondrial RNA knockdown and has a functional impact on mitochondria. Here, we summarize the current state of mitochondrial DDS focusing on our research and show some examples of mitochondrial functional regulations using mitochondrial DDS.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Bangham AD, Horne RW (1964) Negative staining of phospholipids and their structural modification by surface-active agents as observed in the electron microscope. J Mol Biol 8:660–668

    Article  CAS  PubMed  Google Scholar 

  • Biswas S, Torchilin VP (2014) Nanopreparations for organelle-specific delivery in cancer. Adv Drug Deliv Rev 66:26–41

    Article  CAS  PubMed  Google Scholar 

  • Furukawa R, Yamada Y, Takenaga M, Igarashi R, Harashima H (2011) Octaarginine-modified liposomes enhance the anti-oxidant effect of Lecithinized superoxide dismutase by increasing its cellular uptake. Biochem Biophys Res Commun 404(3):796–801

    Article  CAS  PubMed  Google Scholar 

  • Furukawa R, Yamada Y, Kawamura E, Harashima H (2015) Mitochondrial delivery of antisense RNA by MITO-Porter results in mitochondrial RNA knockdown, and has a functional impact on mitochondria. Biomaterials 57:107–115

    Article  CAS  PubMed  Google Scholar 

  • Futaki S, Suzuki T, Ohashi W, Yagami T, Tanaka S, Ueda K, Sugiura Y (2001) Arginine-rich peptides. An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery. J Biol Chem 276(8):5836–5840

    Article  CAS  PubMed  Google Scholar 

  • Goto Y, Nonaka I, Horai S (1990) A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 348(6302):651–653

    Article  CAS  PubMed  Google Scholar 

  • Igarashi R, Hoshino J, Takenaga M, Kawai S, Morizawa Y, Yasuda A, Otani M, Mizushima Y (1992) Lecithinization of superoxide dismutase potentiates its protective effect against Forssman antiserum-induced elevation in guinea pig airway resistance. J Pharmacol Exp Ther 262(3):1214–1219

    CAS  PubMed  Google Scholar 

  • Kajimoto K, Sato Y, Nakamura T, Yamada Y, Harashima H (2014) Multifunctional envelope-type nano device for controlled intracellular trafficking and selective targeting in vivo. J Control Release 190C:593–606

    Article  Google Scholar 

  • Kawamura E, Yamada Y, Harashima H (2013a) Mitochondrial targeting functional peptides as potential devices for the mitochondrial delivery of a DF-MITO-Porter. Mitochondrion 13(6):610–614

    Article  CAS  PubMed  Google Scholar 

  • Kawamura E, Yamada Y, Yasuzaki Y, Hyodo M, Harashima H (2013b) Intracellular observation of nanocarriers modified with a mitochondrial targeting signal peptide. J Biosci Bioeng 116(5):634–637

    Article  CAS  PubMed  Google Scholar 

  • Khalil IA, Kogure K, Futaki S, Harashima H (2006) High density of octaarginine stimulates macropinocytosis leading to efficient intracellular trafficking for gene expression. J Biol Chem 281(6):3544–3551

    Article  CAS  PubMed  Google Scholar 

  • Khalil IA, Hayashi Y, Mizuno R, Harashima H (2011) Octaarginine- and pH sensitive fusogenic peptide-modified nanoparticles for liver gene delivery. J Control Release 156(3):374–380

    Article  CAS  PubMed  Google Scholar 

  • Kogure K, Moriguchi R, Sasaki K, Ueno M, Futaki S, Harashima H (2004) Development of a non-viral multifunctional envelope-type nano device by a novel lipid film hydration method. J Control Release 98(2):317–323

    Article  CAS  PubMed  Google Scholar 

  • Oku N, Doi K, Namba Y, Okada S (1994) Therapeutic effect of adriamycin encapsulated in long-circulating liposomes on Meth-A-sarcoma-bearing mice. Int J Cancer 58(3):415–419

    Article  CAS  PubMed  Google Scholar 

  • Sato Y, Nakamura T, Yamada Y, Akita H, Harashima H (2014) Multifunctional enveloped nanodevices (MENDs). Adv Genet 88:139–204

    PubMed  Google Scholar 

  • Schapira AH (2006) Mitochondrial disease. Lancet 368(9529):70–82

    Article  CAS  PubMed  Google Scholar 

  • Shanske S, Moraes CT, Lombes A, Miranda AF, Bonilla E, Lewis P, Whelan MA, Ellsworth CA, DiMauro S (1990) Widespread tissue distribution of mitochondrial DNA deletions in Kearns-Sayre syndrome. Neurology 40(1):24–28

    Article  CAS  PubMed  Google Scholar 

  • Shoffner JM, Lott MT, Lezza AM, Seibel P, Ballinger SW, Wallace DC (1990) Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation. Cell 61(6):931–937

    Article  CAS  PubMed  Google Scholar 

  • Tawaraya Y, Hyodo M, Ara MN, Yamada Y, Harashima H (2014) RNA aptamers for targeting mitochondria using a mitochondria-based SELEX method. Biol Pharm Bull 37(8):1411–1415

    Article  CAS  PubMed  Google Scholar 

  • Tuppen HA, Blakely EL, Turnbull DM, Taylor RW (2010) Mitochondrial DNA mutations and human disease. Biochim Biophys Acta 1797(2):113–128

    Article  CAS  PubMed  Google Scholar 

  • Wallace DC (1999) Mitochondrial diseases in man and mouse. Science 283(5407):1482–1488

    Article  CAS  PubMed  Google Scholar 

  • Weissig V (2011) From serendipity to mitochondria-targeted nanocarriers. Pharm Res 28(11):2657–2668

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y, Harashima H (2008) Mitochondrial drug delivery systems for macromolecule and their therapeutic application to mitochondrial diseases. Adv Drug Deliv Rev 60(13–14):1439–1462

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y, Harashima H (2012) Delivery of bioactive molecules to the mitochondrial genome using a membrane-fusing, liposome-based carrier, DF-MITO-Porter. Biomaterials 33(5):1589–1595

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y, Harashima H (2013) Enhancement in selective mitochondrial association by direct modification of a mitochondrial targeting signal peptide on a liposomal based nanocarrier. Mitochondrion 13(5):526–532

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y, Harashima H (2014) A method for screening mitochondrial fusogenic envelopes for use in mitochondrial drug delivery. Methods Mol Biol 1141:57–66

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y, Harashima H (2015) Targeting the mitochondrial genome via a dual function MITO-Porter: evaluation of mtDNA levels and mitochondrial function. Methods Mol Biol 1265:123–133

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y, Akita H, Kamiya H, Kogure K, Yamamoto T, Shinohara Y, Yamashita K, Kobayashi H, Kikuchi H, Harashima H (2008) MITO-Porter: a liposome-based carrier system for delivery of macromolecules into mitochondria via membrane fusion. Biochim Biophys Acta 1778(2):423–432

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y, Furukawa R, Yasuzaki Y, Harashima H (2011) Dual function MITO-Porter, a nano carrier integrating both efficient cytoplasmic delivery and mitochondrial macromolecule delivery. Mol Ther 19(8):1449–1456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamada Y, Akita H, Harashima H (2012a) Multifunctional envelope-type nano device (MEND) for organelle targeting via a stepwise membrane fusion process. Methods Enzymol 509:301–326

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y, Kawamura E, Harashima H (2012b) Mitochondrial-targeted DNA delivery using a DF-MITO-Porter, an innovative nano carrier with cytoplasmic and mitochondrial fusogenic envelopes. J Nanopart Res 14(8):1013–1027

    Article  Google Scholar 

  • Yamada Y, Nakamura K, Furukawa R, Kawamura E, Moriwaki T, Matsumoto K, Okuda K, Shindo M, Harashima H (2013a) Mitochondrial delivery of bongkrekic acid using a MITO-porter prevents the induction of apoptosis in human HeLa cells. J Pharm Sci 102(3):1008–1015

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y, Hashida M, Hayashi Y, Tabata M, Hyodo M, Ara MN, Ohga N, Hida K, Harashima H (2013b) An approach to transgene expression in liver endothelial cells using a liposome-based gene vector coated with hyaluronic acid. J Pharm Sci 102(9):3119–3127

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y, Tabata M, Yasuzaki Y, Nomura M, Shibata A, Ibayashi Y, Taniguchi Y, Sasaki S, Harashima H (2014) A nanocarrier system for the delivery of nucleic acids targeted to a pancreatic beta cell line. Biomaterials 35(24):6430–6438

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y, Hashida M, Harashima H (2015a) Hyaluronic acid controls the uptake pathway and intracellular trafficking of an octaarginine-modified gene vector in CD44 positive- and CD44 negative-cells. Biomaterials 52:189–198

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y, Nakamura K, Abe J, Hyodo M, Haga S, Ozaki M, Harashima H (2015b) Mitochondrial delivery of Coenzyme Qvia systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver. J Control Release 213:86–95

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y, Fukuda Y, Harashima H (in press) An analysis of membrane fusion between mitochondrial double membranes and MITO-Porter, mitochondrial fusogenic vesicles. Mitochondrion

    Google Scholar 

  • Yasuzaki Y, Yamada Y, Harashima H (2010) Mitochondrial matrix delivery using MITO-Porter, a liposome-based carrier that specifies fusion with mitochondrial membranes. Biochem Biophys Res Commun 397(2):181–186

    Article  CAS  PubMed  Google Scholar 

  • Zhang E, Zhang C, Su Y, Cheng T, Shi C (2011) Newly developed strategies for multifunctional mitochondria-targeted agents in cancer therapy. Drug Discov Today 16(3–4):140–146

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported, in part, by the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO), Japan, and by a Grant-in-Aid for Young Scientists (A) and Scientific Research (B) from the Ministry of Education, Culture, Sports, Science and Technology of Japanese Government (MEXT), the Mochida Memorial Foundation for Medical and Pharmaceutical Research, and the Uehara Memorial Foundation. We also thank Dr. Milton Feather for his helpful advice in writing the manuscript.

Author information

Authors and Affiliations

  1. Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo, 060-0812, Japan

    Yuma Yamada & Hideyoshi Harashima

Authors
  1. Yuma Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hideyoshi Harashima
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hideyoshi Harashima .

Editor information

Editors and Affiliations

  1. Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

    Harpreet Singh

  2. Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Shey-Shing Sheu

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Yamada, Y., Harashima, H. (2016). MITO-Porter for Mitochondrial Delivery and Mitochondrial Functional Analysis. In: Singh, H., Sheu, SS. (eds) Pharmacology of Mitochondria. Handbook of Experimental Pharmacology, vol 240. Springer, Cham. https://doi.org/10.1007/164_2016_4

Download citation

Publish with us

Policies and ethics

Search

Navigation