DJ-1 and hexokinases

National Institute On Aging

Investigators

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Abstract

We have been interested in the relationship between oxidative stress and DJ-1, a rare cause of recessive Parkinson's disease, for several years and have focussed the relationship between oxidative stress and mitochondrial localization. An area of some controversy has been whether DJ-1 is an enzyme. Many other proteins in the DJ-1 superfamily, which extends to almost all species, have readily assayable activities, results for DJ-1 have been ambiguous, with competing claims as to the nature and quantification of activity. In particular, DJ-1 has been proposed to be a deglycase or a glyoxalase and, in either situation, proposed to play a major role in detoxification of damage resulting from oxidative stress and therefore associated with aging. We addressed this hypothesis using both recombinant enzyme approaches and a number of genetically edited models. Our results clearly show that the deglycase activity of DJ-1 is modest, but that we do see significant accumulation of oxidative damage in cells and tissue. Overall, our work indicate that DJ-1 is likely involved in some aspect of the regulation of responses to macromolecular damage but that additional work is needed to clarify the molecular mechanisms by which it does so.