| Mitochondria utilize electron transfer through the respiratory chain complexes of the inner membrane to create a proton-motive transmembrane potential which drives ATP synthesis by the F1F0 ATP synthase. However, despite this critical bioenergetic role, it remains unclear how this respiratory function is related to mitochondrial structure. While classical biochemical and cell biological studies have provided the framework for understanding mitochondrial form and function, advances in subcellular imaging have revealed that mitochondrial organization is more complex than previously appreciated. In particular, Perkins et al. (1) have shown that the mitochondrial inner membrane system is composed of the cristal and inner boundary membranes. This suggests that the cristal membrane forms a compartment uniquely adapted for mitochondrial respiration. Here I present my research exploring the relationship between mitochondrial internal structure and respiratory function. Experiments examining the distribution of key mitochondrial enzyme complexes confirm the compartmentation of mitochondrial respiratory function, revealing the cristal membrane to be a unique suborganellar compartment specialized for oxidative phosphorylation. By examining mitochondrial structural changes elicited by varying levels of respiratory activity in cultured human cells, these studies further demonstrate the dramatic consequences that cristal compartmentation has for mitochondrial structure. Collectively, these studies demonstrate a hand-in-hand relationship between mitochondrial structure and respiratory function, centered upon the cristal membrane as a specialized, highly responsive membrane system. This dissertation includes my previously published and co-authored material. |
