The role of formate in combatting oxidative stress.

Abstract

As all aerobic organisms are exposed to oxidative stress, they are known to devise intricate mechanisms to counter reactive oxygen species (ROS). Metabolic networks contributing to the production of ketoacids are prominent in alleviating the oxidative burden. When glyoxylate detoxifies ROS, formate is the principal by-product generated. In this study the contribution of formate in enabling the survival of the microbe Pseudomonas fluorescens challenged by hydrogen peroxide (H2O2) has been elucidated. When grown in the presence of H2O2 (stressed culture), the levels of formate were higher in the spent fluid and the soluble cell-free extracts compared to the controls. Formate was subsequently utilized as a reducing factor to produce NADPH and succinate. The former is mediated by formate dehydrogenase (FDH-NADP), whose activity was enhanced in the stressed cells. Fumarate reductase (FRD) that catalyzes the conversion of fumarate into succinate was also markedly increased in the stressed cells. Metabolic adaptation is a pivotal tool in combatting oxidative stress. Formate, a by-product of glyoxylate- mediated detoxification of ROS is recuperated as a potent reductive fuel. It is becoming quite evident that this simple metabolite has other biological roles that have not been fully appreciated.