A collaborative study published in the March 20 issue of the online, open access journal PLoS Biology, reveals that scientists from the Baylor College of Medicine (BCM) and the Montreal Neurological Institute of McGill University have discovered that neurodegenerative disorders that occur in both fruit flies and humans are caused by mutations in the same gene that encodes part of the vital machinery of the mitochondrion.

During an examination of various mutant fruit flies for defects leading to progressive degeneration of photoreceptors in the flies' eye, Vafa Bayat, a recent graduate from the Program in Developmental Biology at BCM and his team discovered mutations in the fruit fly gene that encode a mitochondrial enzyme called the mitochondrial methionyl-tRNA synthetase (Aats-met) that decreases life span and causes other problems, such as lower cell proliferation.

Mitochondria are sometimes described as "cellular power plants", due to the fact that they produce most of the cell's supply of adenosine triphosphate (ATP), which is used as a source of chemical energy. However, they are also involved in processes, such as signaling, cellular differentiation, cell death and regulating cell cycles and cell growth.

Defective genes that encode mitochondrial proteins are also known to implicate human metabolic and neurological disorders.

Dr. Bayat, and his team checked medical literature for genetic neurological disorders, which scientists thought were caused by defects in the region of the genome that contains the human version of the Aats-met gene, MARS2.

Dr. Bernard Brais and team had already mapped one such disease to this region of the genome, i.e. Autosomal Recessive Spastic Ataxia with frequent Leukoencephalopathy (ARSAL). However they failed to identify the precise gene responsible. Ataxias, like ARSAL, are progressive neurodegenerative diseases, which amongst other problems cause coordination difficulties that result in modified gait and speech.

The Montreal team, led by Dr. Isabelle Thiffault, discovered that in ARSAL patients the genetic material of the MARS2 gene is comprehensively rearranged, which resulted in reduced levels of the MARS2 enzyme, reduced synthesis of proteins by the mitochondria, and impaired mitochondrial function. Similar to the fruit fly mutants, the patients' cells also displayed higher levels of reactive oxygen species that can cause damage to cells and their genetic material, as well as slow cell proliferation.

Dr. Bayat said:

"We found the same defect in the mitochondrial respiratory chains in the human cells, which produced a lot of reactive oxygen species. When we feed the fly larvae antioxidants, they suppress the degenerative phenotypes in flies."

Given the ability that antioxidants in flies are able to counteract the negative consequences of the mutant gene, leaves researchers to speculate that it could be possible that a similar approach may also be beneficial in humans. However, this would be subject to further research.

Dr. Bellen concludes:

"While the discovery of mutations in fly genes has been linked to human disease before, it has often taken many years to decades to accomplish this. This was a relatively quick process. In summary, we have shown that you can use flies to identify fly mutants with neurodegenerative phenotypes and that these mutants can assist in the identification of human disease genes."

Written by Petra Rattue