Introduction to mitochondrial function and genomics

In virtually all plant and animal cells, mitochondria are the primary providers of energy but also are the major producers of free radicals and important inducers of programmed cell death pathways. As such, mitochondria are crucial to the proper growth and functioning of the cell, but they also play fundamental roles in numerous pathologic conditions when they become dysfunctional. Mitochondria contain their own DNA, but because they are solely inherited maternally, contain multiple copies of the genome, and replicate independently of cell division, mitochondrial genetics is more akin to population genetics than the Mendelian genetics characteristic of the nuclear genome. Oxidation reactions in the core of the mitochondria yield electrons that are passed sequentially through three respiratory complexes in the inner mitochondrial membrane to generate potential energy for ATP formation. Although numerous diseases are associated with well-defined mutations in the mitochondrial genome, the etiology of the dysfunction in the respiratory complexes characteristic of Alzheimer's and Parkinson's diseases (defects in Complexes IV and I, respectively) is still under investigation. Regardless of underlying cause, improving mitochondrial function represents a novel therapeutic strategy in late-onset, sporadically occurring degenerative diseases such as Alzheimer's. Moreover, elucidating mechanisms that contribute to mitochondrial dysfunction will provide avenues for development of better therapeutic and diagnostic tools for these diseases. Drug Dev. Res. 46:2–13, 1999.