ABSTRACT
In most eukaryotic cells, the DNA genome is housed not only in the nucleus but also in cytoplasmic organelles called mitochondria. The mitochondrion represents a major crossroads of metabolism, being the site for hundreds of essential reactions including those involved in the tricarboxylic acid cycle, fatty acid oxidation, and pathways for the biosynthesis of heme, amino acids, steroid hormones, and many other biochemicals. Of course, mitochondria also perform oxidative phosphorylation (OXPHOS), the process through which the energy derived from the final oxidation of major foodstuffs is efficiently converted to cellular ATP. It is here where the essential function of mitochondrial DNA (mtDNA) is primarily realized, because mtDNA encodes essential protein subunits of the OXPHOS system. Therefore, mutations in mtDNA can result in reduced OXPHOS capacity, declined ATP production, and subsequent loss of proper cell function. While the decline in OXPHOS capacity alone is certainly a very severe negative consequence, the deleterious effects of mitochondrial dysfunction are compounded further by the fact that mitochondria are also a major source of reactive oxygen species (ROS) that can damage cellular components, the production of which is often enhanced under conditions where OXPHOS is disabled. Finally, mitochondria are intricately intertwined with the cellular apoptotic pathways that control programmed cell death. Thus, mtDNA mutations and mitochondrial dysfunction can lead to the purposeful or, in some cases, untimely loss of cells from a population or tissue, again potentially exacerbating the cellular effects of mitochondrial dysfunction.
