Abstract

The inner mitochondrial membrane (IMM) is highly folded into cristae, providing the structural platform for the oxidative phosphorylation (OXPHOS) system. While the molecular components of OXPHOS are well-characterized, the role of the IMM's unique geometry in regulating energy conversion efficiency remains a critical question. This study investigates the hypothesis that **membrane curvature** directly controls the efficiency of the OXPHOS system. Using a combination of theoretical modeling and *in vitro* liposome-based reconstitution assays, we demonstrate that high positive curvature, characteristic of the cristae tips, significantly enhances the local proton concentration and directs proton flow from the respiratory chain complexes to the F1Fo-ATP synthase. Specifically, we find that membrane bending near the proton pumps creates a dedicated, confined pathway for proton movement, effectively minimizing proton leakage into the bulk matrix and increasing the **tight coupling** of respiration to ATP synthesis. Furthermore, the presence of ATP synthase dimers, which are known to induce membrane curvature, is shown to be a key structural determinant in this process. These findings provide a novel biophysical mechanism for the regulation of cellular bioenergetics, highlighting the IMM's architecture as an active, functional component that optimizes energy production. This work has significant implications for understanding mitochondrial dysfunction in various human pathologies.