Mitochondrial Uncouplers as Disease Therapeutics

Insights: Events Mitochondrial Uncouplers as Disease Therapeutics

71st Southeastern Regional Meeting of the American Chemical Society (SERMACS)

Mitochondria are responsible for the generation of ATP by coupling nutrient catabolism of dietary carbohydrates and fats with oxidative phosphorylation. Small molecules capable of shuttling protons from the mitochondrial inner membrane space to the mitochondrial matrix, known as mitochondrial uncouplers, make ATP production inefficient in that more nutrient oxidation is required. Uncouplers have shown promise in treating metabolic diseases such as obesity, type 2 diabetes, ischemia-reperfusion injury and neurodegenerative diseases. Small molecule uncouplers, such as 2,4-dinitrophenol, have been previously shown effective as weight loss agents, but they suffer from deleterious off-target effects and non-selective membrane depolarization limiting their therapeutic application.