IF1: setting the pace of the F1Fo-ATP synthase

When mitochondrial function is compromised and the mitochondrial membrane potential (Δψ_m) falls below a threshold, the F₁F_o-ATP synthase can reverse, hydrolysing ATP to pump protons out of the mitochondrial matrix. Although this activity can deplete ATP and precipitate cell death, it is limited by the mitochondrial protein IF₁, an endogenous F₁F_o-ATPase inhibitor. IF₁, therefore, preserves ATP at the expense of Δψ_m. Despite a wealth of detailed knowledge on the biochemistry of the interaction of IF₁ and the F₁F_o-ATPase, little is known about its physiological activity. Emerging research suggests that IF₁ has a wider ranging impact on mitochondrial structure and function than previously thought.