The Complex Interaction of Mitochondrial Genetics and Mitochondrial Pathways in Psychiatric Disease

While accounting for only 2% of the body's weight, the brain utilizes up to 20% of the body's total energy. Not surprisingly, metabolic dysfunction and energy supply-and-demand mismatch have been implicated in a variety of neurological and psychiatric disorders. Mitochondria are responsible for providing the brain with most of its energetic demands, and the brain uses glucose as its exclusive energy source. Exploring the role of mitochondrial dysfunction in the etiology of psychiatric disease is a promising avenue to investigate further. Genetic analysis of mitochondrial activity is a cornerstone in understanding disease pathogenesis related to metabolic dysfunction. In concert with neuroimaging and pathological study, genetics provides an important bridge between biochemical findings and clinical correlates in psychiatric disease. Mitochondrial genetics has several unique aspects to its analysis, and corresponding special considerations. Here, we review the components of mitochondrial genetic analysis - nuclear DNA, mitochon-drial DNA, mitochondrial pathways, pseudogenes, nuclear-mitochondrial mismatch, and microRNAs - that could contribute to an observable clinical phenotype. Throughout, we highlight psychiatric diseases that can arise due to dysfunction in these processes, with a focus on schizophrenia and bipolar disorder.