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

EMBO J. 2023 May 15;42(10):e114141. doi: 10.15252/embj.2023114141. Epub 2023 Apr 6.

Abstract

The mitochondrial F1 Fo -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.

MeSH terms

  • Adenosine Triphosphate*
  • Mitochondria / metabolism
  • Mitochondrial Proton-Translocating ATPases* / metabolism
  • Protons

Substances

  • Mitochondrial Proton-Translocating ATPases
  • Adenosine Triphosphate
  • Protons