Gene may ‘bypass’ disease-linked mitochondrial defects, fly study suggests

FlyBy lending them a gene normally reserved for other classes of animals, researchers have shown they can rescue flies from their Parkinson’s-like symptoms, including movement defects and excess free radicals produced in power-generating cellular components called mitochondria. The gene swap also protects healthy flies’ mitochondria, and to a large extent the flies themselves, from the damaging effects of cyanide and other toxins, the team reports in the May issue of Cell Metabolism, a Cell Press publication.

The key gene (single-subunit alternative oxidase or AOX) in essence acts as a bypass for blockages in the so-called oxidative phosphorylation (OXPHOS) cytochrome chain in mitochondria. Howard Jacobs, who led the study at the University of Tampere in Finland, likens that chain to a series of waterfalls in a hydroelectric power station. Only, in the case of mitochondria, it is electrons that flow to release energy that is captured in molecular form.

"This is the first whole organism test for the idea that you can take a gene that encodes a single polypeptide and bypass OXPHOS where it is blocked," said Jacobs, emphasizing that OXPHOS includes dozens of components and hundreds of proteins. "You may lose power from one [molecular] ‘turbine,’ but power from the others can be restored. With a single peptide, you can bypass two-thirds of the system. That’s the beauty of the idea."

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