Abnormal Mitochondria in a Non-human Primate Model of MPTP-induced Parkinson's Disease: Drp1 and CDK5/p25 Signaling
- Author:
Junghyung PARK
1
;
Jincheol SEO
;
Jinyoung WON
;
Hyeon Gu YEO
;
Yu Jin AHN
;
Keonwoo KIM
;
Yeung Bae JIN
;
Bon Sang KOO
;
Kyung Seob LIM
;
Kang Jin JEONG
;
Philyong KANG
;
Hwal Yong LEE
;
Seung Ho BAEK
;
Chang Yeop JEON
;
Jung Joo HONG
;
Jae Won HUH
;
Young Hyun KIM
;
Sang Je PARK
;
Sun Uk KIM
;
Dong Seok LEE
;
Sang Rae LEE
;
Youngjeon LEE
Author Information
- Publication Type:Original Article
- Keywords: Cyclin-dependent kinases; Mitochondria; Mitochondrial dynamics; Non-human primate; Parkinson disease
- MeSH: 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
- From:Experimental Neurobiology 2019;28(3):414-424
- CountryRepublic of Korea
- Language:English
- 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.
