The mitochondrial ATP synthase as an ATP consumer—a surprising therapeutic target

Abstract

The mitochondrial F1Fo‐ATP synthase uses a rotary mechanism to synthesise ATP. This mechanism can, however, also operate in reverse, pumping protons at the expense of ATP, with significant potential implications for mitochondrial and age‐related diseases. In a recent study, Acin‐Perez et al (2023) use an elegant assay to screen compounds for the capacity to selectively inhibit ATP hydrolysis without affecting ATP synthesis. They show that (+)‐epicatechin is one such compound and has significant benefits for cell and tissue function in disease models. These findings signpost a novel therapeutic approach for mitochondrial disease.