Anat Cell Biol.  2010 Sep;43(3):179-184. 10.5115/acb.2010.43.3.179.

PINK1 and Parkin to control mitochondria remodeling

• Koh H
• Chung J

• KMID: 2168872
• DOI: http://doi.org/10.5115/acb.2010.43.3.179

Abstract

Parkinson's disease (PD), one of the most common neurodegenerative diseases, is characterized by movement disorders and a loss of dopaminergic (DA) neurons. PD mainly occurs sporadically, but may also result from genetic mutations in several PD-linked genes. Recently, genetic studies with Drosophila mutants, parkin and PINK1, two common PD-associated genes, demonstrated that Parkin acts downstream of PINK1 in maintaining mitochondrial function and integrity. Further studies revealed that PINK1 translocates Parkin to mitochondria and regulates critical mitochondrial remodeling processes. These findings, which suggest that mitochondrial dysfunction is a prominent cause of PD pathogenesis, provide valuable insights which may aid in the development of effective treatments for PD.

Keyword

PINK1; Parkin; Mitochondria; Parkinson's disease

MeSH Terms

Drosophila
Mitochondria
Movement Disorders
Neurodegenerative Diseases
Neurons
Parkinson Disease

Figure

• 

  Fig. 1 PINK1 mutation induces mitochondrial defects. Drosophila PINK1 mutants (B9) demonstrated the crushed-thorax phenotype (top panel, white arrows), an indicator of flight muscle degeneration, and mitochondrial swelling in indirect flight muscles (middle panel) and DA neurons (bottom panel). Toluidine blue staining of longitudinal thorax sections revealed mitochondrial morphology of indirect flight muscles (middle panel). Expression of mitochondria-targeted green fluorescent protein (mito-GFP, green) showed mitochondria shape and size in the DA neurons of adult fly brains (bottom panel). Wild type controls (WT) showed an intact thorax structure and mitochondrial morphology. Scale bar=yellow, 5 µm.

• 

  Fig. 2 Transgenic expression of parkin ameliorates PINK1 mutant phenotypes, but not vice versa. Over-expression of parkin successfully rescued mitochondrial swelling, mtDNA content, and ATP levels in PINK1 mutants. However, the PINK1 transgene failed to restore these defects in parkin mutants. (A) Mitochondria in indirect flight muscles from PINK1 mutants (B9), Parkin-expressing PINK1 mutants (B9, parkin), parkin mutants (park1), and PINK1-expressing parkin mutants (park1, PINK1). (B) Quantification of mtDNA in fly thoraces. Quantitative real-time PCR was performed using primers from the mtDNA sequences of the following mitochondrial genes: Cox I, cytochrome c oxidase subunit I; Cox III, cytochrome c oxidase subunit III; Cyt B, cytochrome b. Results are expressed as fold change compared relative to WT controls. (C) Comparison of ATP content in fly thoraces. The relative ATP level was calculated by dividing the measured ATP concentration by the total protein concentration. In mtDNA and ATP assays, averages±SDs are from three experiments. Significance was determined by one-way ANOVA (*P<0.01; NS, not significant). Error bars indicate mean±SD. Scale bar=yellow, 5 µm.

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