Exp Neurobiol.  2019 Jun;28(3):414-424. 10.5607/en.2019.28.3.414.

Abnormal Mitochondria in a Non-human Primate Model of MPTP-induced Parkinson's Disease: Drp1 and CDK5/p25 Signaling

Affiliations
  • 1National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea. srlee@kribb.re.kr, neurosci@kribb.re.kr
  • 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.

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.

Keyword

Cyclin-dependent kinases; Mitochondria; Mitochondrial dynamics; Non-human primate; Parkinson disease

MeSH Terms

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Cyclin-Dependent Kinase 5
Cyclin-Dependent Kinases
Dopaminergic Neurons
Homeostasis
Mitochondria*
Mitochondrial Dynamics
Neurodegenerative Diseases
Parkinson Disease*
Phosphorylation
Phosphotransferases
Primates*
Substantia Nigra
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Cyclin-Dependent Kinase 5
Cyclin-Dependent Kinases
Phosphotransferases
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