Sign In
Register
eISSN:2278-5299

International Journal of Latest Research in Science and Technology

DOI:10.29111/ijlrst   ISRA Impact Factor:3.35

A News Letter Sign UP!
PARKINSON?S DISEASE GENE PRODUCT, PARKIN, HAS ALTERNATIVE AND REVERSIBLE FUNCTIONS, BOTH AS AN E3 LIGASE AND A REDOX MOLECULE.

Research Paper Open Access

International Journal of Latest Research in Science and Technology Vol.5 Issue 4, pp 20-22,Year 2016

PARKINSON?S DISEASE GENE PRODUCT, PARKIN, HAS ALTERNATIVE AND REVERSIBLE FUNCTIONS, BOTH AS AN E3 LIGASE AND A REDOX MOLECULE.

Tohru Kitada , Rie Hikita, Hideo Hirose

Correspondence should be addressed to :

Received : 29 July 2016; Accepted : 07 August 2016 ; Published : 31 August 2016

Share
Download 126
View 179
Article No. 10669
Abstract

We have recently shown that Parkin reacts with and reduces H2O2, a main component in mitochondrial oxidative stress, and forms Parkin dimer. In this in vitro study, we indicated that H2O2 leads to Parkin autoubiquitination as well as dimerization, and reduces E3 ligase activity in the ubiquitin-proteasome system. However, the antioxidant Dithiothreitol (DTT) decomposes polyubiquitinated Parkin dimers to the monomer level and reactivates Parkin’s E3 ligase activity, resulting in the increase of polyubiquitination of the substrate. Thus, Parkin protein has alternative and reversible functions as an E3 ligase and as a redox molecule to reduce oxidative stress. In other words, Parkin has a unique recycling system.

Key Words   
Parkin, Parkinson’s Disease, Mitochondria, Oxidative Stress, E3 Ligase, Ubiquitination, Pr

Copyright
References
  1. 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. 392(6676):605-608 (1998).
  2. Shimura H, Hattori N, Kubo Si, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka K, Suzuki T. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet. 25(3):302-305 (2000).
  3. Narendra DP, Jin SM, Tanaka A, Suen DF, Gautier CA, Shen J, Cookson MR, Youle RJ. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PloS Biol. 8(1):e1000298. doi:　1371/journal.pbio.1000298 (2010).
  4. Kuroda Y, Sako W, Goto S, Sawada T, Uchida D, Izumi Y, Takahashi T, Kagawa N, Matsumoto M, Matsumoto M, Takahashi R, Kaji R, Mitsui T. Parkin interacts with Klokin1 for mitochondrial import and maintenance of membrane potential. Hum Mol Genet. 21(5):991-1003 (2012).
  5. Kitada T, Hikita R, Hirose H. Parkin, Parkinson disease gene product, directly reduces hydrogen peroxide (mitochondrial oxidant), and forms dimerization reversibly. International Journal of Latest Research in Science and Technology. 5(4):1-3 (2016).
  6. Sul JW, Park MY, Shin J, Kim YR, Yoo SE, Kong YY, Kwon KS, Lee YH, Kim E. Accumulation of the parkin substrate, FAF1, plays a key role in the dopaminergic neurodegeneration. Hum Mol Genet. 22(8):1558-1573 (2013).
  7. Chaugule VK, Burchell L, Barber KR, Sidhu A, Leslie SJ, Shaw GS, Walden H. Autoregulation of Parkin activity through its ubiquitin-like domain. EMBO J. 30(14):2853-2867 (2011).
  8. Yao D, Gu Z, Nakamura T, Shi ZQ, Ma Y, Gaston B, Palmer LA, Rockenstein EM, Zhang Z, Masliah E, Uehara T, Lipton SA. Nitrosative stress linked to sporadic Parkinson's disease: S-nitrosylation of parkin regulates its E3 ubiquitin ligase activity. Proc Natl Acad Sci U S A. 101(29):10810-10814 (2004). Erratum in: Proc Natl Acad Sci U S A. 101(38):13969 (2004).
To cite this article

Tohru Kitada , Rie Hikita, Hideo Hirose , " Parkinson?s Disease Gene Product, Parkin, Has Alternative And Reversible Functions, Both As An E3 Ligase And A Redox Molecule. ", International Journal of Latest Research in Science and Technology . Vol. 5, Issue 4, pp 20-22 , 2016

Responsive image

MNK Publication was founded in 2012 to upholder revolutionary ideas that would advance the research and practice of business and management. Today, we comply with to advance fresh thinking in latest scientific fields where we think we can make a real difference and growth now also including medical and social care, education,management and engineering.

Responsive image

We offers several opportunities for partnership and tie-up with individual, corporate and organizational level. We are working on the open access platform. Editors, authors, readers, librarians and conference organizer can work together. We are giving open opportunities to all. Our team is always willing to work and collaborate to promote open access publication.

Responsive image

Our Journals provide one of the strongest International open access platform for research communities. Our conference proceeding services provide conference organizers a privileged platform for publishing extended conference papers as journal publications. It is deliberated to disseminate scientific research and to establish long term International collaborations and partnerships with academic communities and conference organizers.