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Primordial Gene Might Permit Bypass of Mitochondrial Defects

Researchers have shown that by providing Parkinson-disease-model fruit flies with a gene they don’t normally possess, they can rescue the flies from their Parkinson-like symptoms, including movement defects and excess free radicals produced in mitochondria. The key gene (single-subunit alternative oxidase or AOX) essentially acts as a bypass for blockages in the so-called oxidative phosphorylation (OXPHOS) cytochrome chain in mitochondria. Dr. 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. Defects in mitochondrial OXPHOS are associated with diverse and mostly intractable human disorders, the researchers said. Therefore, there's a chance that the strategy might also prove beneficial in mammals, including humans, which, like insects, have also lost the AOX gene over the course of evolution. On the other hand, most plants, animals, and fungi do possess an alternative mitochondrial respiratory chain, which can bypass the OXPHOS system under specific physiological conditions. Their findings led the researchers to conclude that “AOX appears to offer promise as a wide-spectrum therapeutic tool in OXPHOS disorders.” “OXPHOS dysfunction is not just a problem in some rare genetic disorders or in degenerative diseases,” Dr. Jacobs added. It's an issue in a very large number of pathologies—and a major cause of tissue damage after heart attack and stroke. The next step is to test whether the findings in flies will also hold true in mammals, Dr. Jacobs noted. His hope is that the AOX gene might someday be delivered to humans via a suitable gene therapy, although he admits that goal assumes many things will fall into place. This work was reported in the May issue of Cell Metabolism. [Cell Press release] [Cell Metabolism abstract]