Salidroside Protects Dopaminergic Neurons by Enhancing PINK1/Parkin-Mediated Mitophagy

Parkinson’s disease (PD) is a common neurodegenerative disease characterized by the degeneration of nigrostriatal dopaminergic (DA) neurons. Our previous studies have suggested that salidroside (Sal) might play neuroprotective effects against PD by preserving mitochondrial Complex I activity. However, the exact mechanism of the neuroprotective effect of Sal remains unclear. Growing evidence indicates that PINK1/Parkin-mediated mitophagy is involved in the development of PD. In this study, we investigated whether Sal exerts a neuroprotective effect by modulating PINK1/Parkin-mediated mitophagy. Results showed that Sal alleviated MPTP-induced motor deficits in pole test. Moreover, Sal diminished MPTP-induced degeneration of nigrostriatal DA neurons as evidenced by upregulated TH-positive neurons in the substantia nigra, increased DAT expression, and high dopamine and metabolite levels in the striatum. Furthermore, in comparison with the MPP+/MPTP group, Sal considerably increased the mitophagosome and mitophagy flux. Moreover, in comparison with the MPP+/MPTP group, Sal evidently enhanced the mitochondrial expression of PINK1 and Parkin, accompanied by an increase in the colocalization of mitochondria with Parkin. However, transfection of MN9D cells with PINK1 siRNA reversed Sal-induced activated mitophagy and cytoprotective effect. In conclusion, Sal may confer neuroprotective effects by enhancing PINK1/Parkin-mediated mitophagy in MPP+/MPTP-induced PD models.

Download Full-text

ATP-Sensitive Potassium Channels in Dopaminergic Neurons: Transducers of Mitochondrial Dysfunction

Physiology ◽

10.1152/physiologyonline.2001.16.5.214 ◽

2001 ◽

Vol 16 (5) ◽

pp. 214-217 ◽

Cited By ~ 2

Author(s):

Birgit Liss ◽

Jochen Roeper

Keyword(s):

Electrical Activity ◽

Mitochondrial Dysfunction ◽

Dopaminergic Neurons ◽

Complex I ◽

Mitochondrial Complex I ◽

Mitochondrial Complex ◽

Midbrain Neurons ◽

Channel Expression ◽

A Cell ◽

Complex I Activity

ATP-sensitive potassium (KATP) channels directly couple the metabolic state of a cell to its electrical activity. Dopaminergic midbrain neurons express alternative types of KATP channels mediating their differential response to mitochondrial complex I inhibition. Because reduced complex I activity is present in Parkinson's Disease, differential KATP channel expression suggests a novel candidate mechanism for selective dopaminergic degeneration.

Download Full-text

Faculty Opinions recommendation of PINK1 loss-of-function mutations affect mitochondrial complex I activity via NdufA10 ubiquinone uncoupling.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718319149.793497763 ◽

2014 ◽

Author(s):

Ted Dawson ◽

Sheila Pirooznia

Keyword(s):

Complex I ◽

Mitochondrial Complex I ◽

Loss Of Function ◽

Mitochondrial Complex ◽

Complex I Activity

Download Full-text

CD147 Interacts with NDUFS6 in Regulating Mitochondrial Complex I Activity and the Mitochondrial Apoptotic Pathway in Human Malignant Melanoma Cells

Current Molecular Medicine ◽

10.2174/1566524014666141202144601 ◽

2014 ◽

Vol 14 (10) ◽

pp. 1252-1264 ◽

Cited By ~ 18

Author(s):

Z. Luo ◽

W. Zeng ◽

W. Tang ◽

T. Long ◽

J. Zhang ◽

...

Keyword(s):

Malignant Melanoma ◽

Complex I ◽

Melanoma Cells ◽

Mitochondrial Complex I ◽

Mitochondrial Complex ◽

Apoptotic Pathway ◽

Human Malignant Melanoma ◽

Mitochondrial Apoptotic Pathway ◽

Complex I Activity

Download Full-text

Effect of feeding malnourished patients for 1 mo on mitochondrial complex I activity and nutritional assessment measurements

American Journal of Clinical Nutrition ◽

10.1093/ajcn/79.5.787 ◽

2004 ◽

Vol 79 (5) ◽

pp. 787-794 ◽

Cited By ~ 12

Author(s):

Francoise Briet ◽

Clare Twomey ◽

Khursheed N Jeejeebhoy

Keyword(s):

Complex I ◽

Nutritional Assessment ◽

Mitochondrial Complex I ◽

Mitochondrial Complex ◽

Complex I Activity ◽

Effect Of Feeding

Download Full-text

CFM6 is an Essential CRM Protein Required for the Splicing of nad5 Transcript in Arabidopsis Mitochondria

Plant and Cell Physiology ◽

10.1093/pcp/pcab161 ◽

2021 ◽

Author(s):

Wei-Chih Lin ◽

Ya-Huei Chen ◽

Shin-Yuan Gu ◽

Hwei-Ling Shen ◽

Kai-Chau Huang ◽

...

Keyword(s):

Complex I ◽

Mitochondrial Complex I ◽

Mitochondrial Complex ◽

High Accumulation ◽

Stunted Growth ◽

Growth Defects ◽

Group I ◽

Or Genes ◽

Complex I Activity ◽

Intron 4

Abstract Plant CRM domain-containing proteins are capable of binding RNA to facilitate the splicing of group I or II introns in chloroplasts, but their functions in mitochondria are less clear. In the present study, Arabidopsis thaliana CFM6, a protein with a single CRM domain, was expressed in most plant tissues, particularly in flower tissues, and restricted to mitochondria. Mutation of CFM6 causes severe growth defects, including stunted growth, curled leaves, delayed embryogenesis, and pollen development. CFM6 functions specifically in the splicing of group II intron 4 of nad5, which encodes a subunit of mitochondrial complex I, as evidenced by the loss of nad5 intron 4 splicing and high accumulation of its pretranscripts in cfm6 mutants. The phenotypic and splicing defects of cfm6 were rescued in transgenic plants overexpressing 35S::CFM6-YFP. Splicing failure in cfm6 also led to the loss of complex I activity and to its improper assembly. Moreover, dysfunction of complex I induced the expression of proteins or genes involved in alternative respiratory pathways in cfm6. Collectively, CFM6, a previously uncharacterized CRM domain-containing protein, is specifically involved in the cis-splicing of nad5 intron 4 and plays a pivotal role in mitochondrial complex I biogenesis and normal plant growth.

Download Full-text