Structure and function of mitochondria: their organization and disorders.

In this lecture, recent advances in studies on the structure and function of mitochondria were reviewed. In particular, in order to understand the etiology of mitochondrial myopathies, the mechanism of the biogenesis of the mitochondrial structure with proteins synthesized in mitochondria and in the cytoplasm was discussed; namely, how proteins encoded by mitochondrial DNA are biosynthesized, and how nuclealy encoded proteins are targeted into the appropriate compartments inside the mitochondria. Recent advances in mitochondriology have made it possible to isolate and purify the enzyme complexes and their subunits, which are involved in mitochondrial oxidative phosphorylation. Immunochemical analyses using a specific antibody against each complex or subunit enabled us to detect defects in individual subunits in mitochondria isolated from a small amount of biopsied material. Several examples of molecular defects revealed by these methods in patients with mitochondrial myopathies were presented, and the principles of their therapy are discussed on the basis of the pattern of the defect. Specific antibodies are also a powerful tool for the cloning of the human cDNAs for the subunits in the mitochondrial energy-transducing machinery. This approach will hopefully facilitate elucidation of the genetic defects underlying these disorders.