RGD Reference Report - The PINK1/Parkin pathway regulates mitochondrial dynamics and function in mammalian hippocampal and dopaminergic neurons. - Rat Genome Database

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The PINK1/Parkin pathway regulates mitochondrial dynamics and function in mammalian hippocampal and dopaminergic neurons.

Authors: Yu, Wendou  Sun, Yaping  Guo, Su  Lu, Bingwei 
Citation: Yu W, etal., Hum Mol Genet. 2011 Aug 15;20(16):3227-40. doi: 10.1093/hmg/ddr235. Epub 2011 May 25.
RGD ID: 12903967
Pubmed: PMID:21613270   (View Abstract at PubMed)
PMCID: PMC3140825   (View Article at PubMed Central)
DOI: DOI:10.1093/hmg/ddr235   (Journal Full-text)

PTEN-induced putative kinase 1 (PINK1) and Parkin act in a common pathway to regulate mitochondrial dynamics, the involvement of which in the pathogenesis of Parkinson's disease (PD) is increasingly being appreciated. However, how the PINK1/Parkin pathway influences mitochondrial function is not well understood, and the exact role of this pathway in controlling mitochondrial dynamics remains controversial. Here we used mammalian primary neurons to examine the function of the PINK1/Parkin pathway in regulating mitochondrial dynamics and function. In rat hippocampal neurons, PINK1 or Parkin overexpression resulted in increased mitochondrial number, smaller mitochondrial size and reduced mitochondrial occupancy of neuronal processes, suggesting that the balance of mitochondrial fission/fusion dynamics is tipped toward more fission. Conversely, inactivation of PINK1 resulted in elongated mitochondria, indicating that the balance of mitochondrial fission/fusion dynamics is tipped toward more fusion. Furthermore, overexpression of the fission protein Drp1 (dynamin-related protein 1) or knocking down of the fusion protein OPA1 (optical atrophy 1) suppressed PINK1 RNAi-induced mitochondrial morphological defect, and overexpression of PINK1 or Parkin suppressed the elongated mitochondria phenotype caused by Drp1 RNAi. Functionally, PINK1 knockdown and overexpression had opposite effects on dendritic spine formation and neuronal vulnerability to excitotoxicity. Finally, we found that PINK1/Parkin similarly influenced mitochondrial dynamics in rat midbrain dopaminergic neurons. These results, together with previous findings in Drosophila dopaminergic neurons, indicate that the PINK1/Parkin pathway plays conserved roles in regulating neuronal mitochondrial dynamics and function.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of mitochondrial fission  IMP 12903967 RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
mitochondria dynamics pathway   IMP 12903967 RGD 
mitochondria fusion pathway  ISOOpa1 (Rattus norvegicus)12903967; 12903967 RGD 
mitochondria fusion pathway  IMP 12903967 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Opa1  (OPA1, mitochondrial dynamin like GTPase)
Pink1  (PTEN induced kinase 1)

Genes (Mus musculus)
Opa1  (OPA1, mitochondrial dynamin like GTPase)

Genes (Homo sapiens)
OPA1  (OPA1 mitochondrial dynamin like GTPase)


Additional Information