How does density of the inner mitochondrial membrane influence mitochondrial performance?

Our current understanding of variation in mitochondrial performance is incomplete. The production of ATP via oxidative phos-phorylation is dependent, in part, on the structure of the inner mitochondrial membrane. Morphology of the inner membrane is crucial for the formation of the proton gradient across the inner membrane and, therefore, ATP synthesis. The inner mitochon-drial membrane is dynamic, changing shape and surface area. These changes alter density (amount per volume) of the inner mi-tochondrial membrane within the confined space of the mitochondrion. Because the number of electron transport system proteins within the inner mitochondrial membrane changes with inner mitochondrial membrane area, a change in the amount of inner membrane alters the capacity for ATP production within the organelle. This review outlines the evidence that the associa-tion between ATP synthases, inner mitochondrial membrane density, and mitochondrial density (number of mitochondria per cell) impacts ATP production by mitochondria. Furthermore, we consider possible constraints on the capacity of mitochondria to produce ATP by increasing inner mitochondrial membrane density.