Mitochondrial uncouplers induce proton leak by activating AAC and UCP1.

ABSTRACT: Mitochondria generate heat due to H⁺ leak (I_H) across their inner membrane¹. I_H results from the action of long-chain fatty acids on uncoupling protein 1 (UCP1) in brown fat^2-6 and ADP/ATP carrier (AAC) in other tissues^1,7-9, but the underlying mechanism is poorly understood. As evidence of pharmacological activators of I_H through UCP1 and AAC is lacking, I_H is induced by protonophores such as 2,4-dinitrophenol (DNP) and cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP)^10,11. Although protonophores show potential in combating obesity, diabetes and fatty liver in animal models^12-14, their clinical potential for treating human disease is limited due to indiscriminately increasing H

SUBMITTER: Bertholet AM 

PROVIDER: S-EPMC9646675 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature