An engineered enzyme that targets circulating lactate to alleviate intracellular NADH:NAD⁺ imbalance.

ABSTRACT: An elevated intracellular NADH:NAD⁺ ratio, or 'reductive stress', has been associated with multiple diseases, including disorders of the mitochondrial electron transport chain. As the intracellular NADH:NAD⁺ ratio can be in near equilibrium with the circulating lactate:pyruvate ratio, we hypothesized that reductive stress could be alleviated by oxidizing extracellular lactate to pyruvate. We engineered LOXCAT, a fusion of bacterial lactate oxidase (LOX) and catalase (CAT), which irreversibly converts lactate and oxygen to pyruvate and water. Addition of purified LOXCAT to the medium of cultured human cells with a defective electron transport chain decreased the extracellular lactate:pyruvate ratio, normalized the intracellular NADH:NAD⁺ ratio, upregulated g

SUBMITTER: Patgiri A 

PROVIDER: S-EPMC7135927 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature