Exploration of the Molybdenum Cofactor gene in the fruit fly Drosophila melangoster

Molybdenum (Mo) is an essential trace metal found in most foods. Enzymes that require Mo cannot use this metal unless it is chelated with an organic complex called the Mo cofactor. MOCS1 is a gene that encodes an enzyme that catalyzes the first step in the synthesis of the Mo Cofactor ('MoCo'). The MOCS1 gene is extremely highly conserved, found in bacteria, fungi, plants and animals. Mutations in MOCS1 cause a disease in humans known as Molybdenum cofactor (MoCo) deficiency, which ultimately results in a combined deficiency of three essential enzymatic functions that depend on Mo: sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase. These enzymes confer a protective function on the cell, by removing toxic catabolites. Sulfite oxidase, for example, is located in the mitochondrial intermembrane space, where it catalyzes the oxidation of sulfite to sulfate, removing the reactive and potentially toxic sulfite from the cell. MoCo deficiency segregates as an autosomal recessive disorder, and generally leads to early childhood death. We hypothesize that an increase in MOCS1 gene expression may have protective effects, by permitting the enzymes that depend on Mo and its cofactor to function more efficiently. Life extending strategies in model organisms have been successful when targeting similar protective pathways that also involve mitochondrial function. The work presented here outlines the preparatory phase of a longevity experiment, in which we plan to upregulate MOCS1 gene expression in fruit flies, and measure the effect on lifespan.