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PMID:16818890

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Citation

Yang, Y, Gehrke, S, Imai, Y, Huang, Z, Ouyang, Y, Wang, JW, Yang, L, Beal, MF, Vogel, H and Lu, B (2006) Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin. Proc. Natl. Acad. Sci. U.S.A. 103:10793-8

Abstract

Mutations in Pink1, a gene encoding a Ser/Thr kinase with a mitochondrial-targeting signal, are associated with Parkinson's disease (PD), the most common movement disorder characterized by selective loss of dopaminergic neurons. The mechanism by which loss of Pink1 leads to neurodegeneration is not understood. Here we show that inhibition of Drosophila Pink1 (dPink1) function results in energy depletion, shortened lifespan, and degeneration of select indirect flight muscles and dopaminergic neurons. The muscle pathology was preceded by mitochondrial enlargement and disintegration. These phenotypes could be rescued by the wild type but not the pathogenic C-terminal deleted form of human Pink1 (hPink1). The muscle and dopaminergic phenotypes associated with dPink1 inactivation show similarity to that seen in parkin mutant flies and could be suppressed by the overexpression of Parkin but not DJ-1. Consistent with the genetic rescue results, we find that, in dPink1 RNA interference (RNAi) animals, the level of Parkin protein is significantly reduced. Together, these results implicate Pink1 and Parkin in a common pathway that regulates mitochondrial physiology and cell survival in Drosophila.

Links

PubMed PMC1502310 Online version:10.1073/pnas.0602493103

Keywords

Animals; Animals, Genetically Modified; Drosophila Proteins/genetics; Drosophila Proteins/physiology; Drosophila melanogaster/genetics; Gene Silencing; Humans; Mitochondria/pathology; Muscles/pathology; Muscles/physiopathology; Nerve Degeneration/genetics; Nerve Degeneration/pathology; Nerve Degeneration/physiopathology; Neurons/pathology; Parkinson Disease; Protein Kinases/deficiency; Protein Kinases/genetics; RNA Interference; Signal Transduction/genetics; Ubiquitin-Protein Ligases

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:PINK1

involved_in

GO:0007005: mitochondrion organization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:PINK1

involved_in

GO:0043524: negative regulation of neuron apoptotic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q961J3

involved_in

GO:0043524: negative regulation of neuron apoptotic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q961J3

involved_in

GO:0007005: mitochondrion organization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q0KHV6

involved_in

GO:0007005: mitochondrion organization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q0KHV6

involved_in

GO:0043524: negative regulation of neuron apoptotic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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