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KMID : 0892920190280030414
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Experimental Neurobiology
2019 Volume.28 No. 3 p.414 ~ p.424
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Abnormal Mitochondria in a Non-human Primate Model of MPTP-induced Parkinson's Disease: Drp1 and CDK5/p25 Signaling
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Park Jung-Hyung
Seo Jin-Cheol
Won Jin-Young
Yeo Hyeon-Gu
Ahn Yu-Jin
Kim Keon-Woo
Jin Yeung-Bae
Koo Bon-Sang
Lim Kyung-Seob
Jeong Kang-Jin
Kang Phil-Yong
Lee Hwal-Yong
Baek Seung-Ho
Jeon Chang-Yeop
Hong Jung-Joo
Huh Jae-Won
Kim Young-Hyun
Park Sang-Je
Kim Sun-Uk
Lee Dong-Seok
Lee Sang-Rae
Lee Young-Jeon
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Abstract
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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.
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KEYWORD
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Cyclin-dependent kinases, Mitochondria, Mitochondrial dynamics, Non-human primate, Parkinson disease
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