Mitochondrial oxidative phosphorylation (OX-PHOS) produces the majority of the cellular energy (ATP) required for normal function in a variety of organs and tissues. Because both mitochondrial and nuclear genomes encode the genes required for OXPHOS, its genetics are complex. Moreover, the novel features of mitochondrial genetics provide an alternative means for interpreting some forms of heterogeneous genetic disease. A prediction of the mitochondrial genetic paradigm is that some forms of chronic degenerative disease will be due to mitochondrial DNA mutations. Recent studies have confirmed this notion by showing that mutations in the mitochondrial DNA can be responsible for diabetes mellitus. © 1995 by Williams and Wilkins.