When mitochondrial function is compromised and the mitochondrial membrane potential (Deltapsi(m)) falls below a threshold, the F(1)F(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 IF(1), an endogenous F(1)F(o)-ATPase inhibitor. IF(1), therefore, preserves ATP at the expense of Deltapsi(m). Despite a wealth of detailed knowledge on the biochemistry of the interaction of IF(1) and the F(1)F(o)-ATPase, little is known about its physiological activity. Emerging research suggests that IF(1) has a wider ranging impact on mitochondrial structure and function than previously thought.