Parkinson's gene linked to mitochondrial function in fruit flies

[unseennude]

Mutant forms of the PINK1 gene, which have been implicated in Parkinson's disease, cause mitochondrial dysfunction in Drosophila melanogaster, according to the findings of two studies appearing in the May 3rd online issue of Nature.

In one study, Dr. Ming Guo, from the University of California at Los Angeles, and colleagues assessed the effect of removing the Drosophila PINK1 homologue.

This alteration led to fruit flies with abnormally shaped mitochondria, apoptotic muscle degeneration, heightened sensitivity to oxidative and other forms of stress, and male sterility. Further testing showed that pink1 localizes to mitochondria and linked pink1 mutants with fragmented mitochondrial cristae.

Introducing the human form of PINK1 into the mutated flies restored the normal mitochondrial shape as well as male fertility.

Loss of Parkin, another gene that has been tied to Parkinson's disease, caused similar changes as the PINK1 deficit. In addition, overexpression of Parkin corrected the abnormalities seen with PINK1 loss, but not vice-versa, suggesting that PINK1 functions upstream of Parkin.

In a similar study, Dr. Jongkyeoung Chung, from the Korea Advanced Institute of Science and Technology in Taejon, and colleagues created fruit flies with loss-of-function PINK1 mutants.

The presence of these mutants was associated with mitochondrial dysfunction, motor disturbances, and dopaminergic neurodegeneration.

As in the first study, the PINK1 mutants produced phenotypic changes similar to those seen with Parkin mutants. Once again, Parkin overexpression corrected the effects of PINK1 mutation, whereas the opposite was not seen.

"The role of the pink1-parkin pathway in regulating mitochondrial function underscores the importance of mitochondrial dysfunction as a central mechanism of Parkinson's disease pathogenesis," Dr. Guo's team concludes.