Articles
Article Tools
 View Full Text |
 Abstract |
 Article as PDF |
 Print this Article |
 Pubmed |
 PMC |
 PubReader |
 Export to Citation |
 Email Alerts |
 Open Access |
Share this article on :
Stats or Metrics
Article
Original Article
Exp Neurobiol 2019; 28(3): 414-424
Published online May 24, 2019
https://doi.org/10.5607/en.2019.28.3.414
© The Korean Society for Brain and Neural Sciences
Abnormal Mitochondria in a Non-human Primate Model of MPTP-induced Parkinson's Disease: Drp1 and CDK5/p25 Signaling
Junghyung Park1,†, Jincheol Seo1,2,†, Jinyoung Won1, Hyeon-Gu Yeo1,3, Yu-Jin Ahn1,3, Keonwoo Kim1,4, Yeung Bae Jin1, Bon-Sang Koo1, Kyung Seob Lim5, Kang-Jin Jeong1, Philyong Kang5, Hwal-Yong Lee1, Seung Ho Baek1, Chang-Yeop Jeon1, Jung-Joo Hong1, Jae-Won Huh1,3, Young-Hyun Kim1,3, Sang-Je Park1, Sun-Uk Kim3,5, Dong-Seok Lee2, Sang-Rae Lee1,3*, and Youngjeon Lee1,3*
1National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea.
2School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Korea.
3Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon 34113, Korea.
4Department of Physical Therapy, Graduate School of Inje University, Gimhae 50834, Korea.
5Futuristic Animal Resource & Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea.
Correspondence to: *To whom correspondence should be addressed.
Sang-Rae Lee, TEL: 82-43-240-6322, FAX: 82-43-240-6309
e-mail: srlee@kribb.re.kr
Youngjeon Lee, TEL: 82-43-240-6316, FAX: 82-43-240-6309
e-mail: neurosci@kribb.re.kr
†These authors contributed equally to work.
Abstract
Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD. Here, we investigated the balance between mitochondrial fusion and fission in the substantia nigra of a non-human primate model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. We found that MPTP induced shorter and abnormally distributed mitochondria. This phenomenon was accompanied by the activation of dynamin-related protein 1 (Drp1), a mitochondrial fission protein, through increased phosphorylation at S616. Thereafter, we assessed for activation of the components of the cyclin-dependent kinase 5 (CDK5) and extracellular signal-regulated kinase (ERK) signaling cascades, which are known regulators of Drp1(S616) phosphorylation. MPTP induced an increase in p25 and p35, which are required for CDK5 activation. Together, these findings suggest that the phosphorylation of Drp1(S616) by CDK5 is involved in mitochondrial fission in the substantia nigra of a non-human primate model of MPTP-induced PD.
Graphical Abstract
Keywords: Cyclin-dependent kinases, Mitochondria, Mitochondrial dynamics, Non-human primate, Parkinson disease
