Mitochondrial morphology and intracellular calcium homeostasis in cytochrome oxidase-deficient human fibroblasts.

Mitochondrial encephalomyopathies arise from mutations in the mitochondrial or nuclear genome and result in defective energy metabolism. Investigation of cellular pathophysiology in these disorders has been limited to nonneuronal explant cultures such as fibroblasts and myoblasts. While investigating mitochondrial structure and function in fibroblasts obtained from control and cytochrome oxidase-deficient (COX) patients, we observed possible abnormalities by vital dye confocal microscopy. Most notable were swelling, reticulation (e.g., intricate fusion of mitochondria), and proliferation of mitochondria. However, a detailed quantitative comparison of mitochondrial morphology in age-, sex-, and passage-matched cultures revealed no significant differences between control and cytochrome oxidase-deficient fibroblasts, nor any differences with passage. In addition, COX fibroblasts exhibited no obvious impairment of intracellular calcium handling, measured by fura-2. These results indicate that cytochrome oxidase deficiency, at the level in these cultures, does not produce structural or ionic concentration alterations in fibroblasts. Future investigation of the pathophysiology of this respiratory chain disorder may require excitable tissue.