Mitochondrial dysfunction and the role of the non-specialist laboratory

Each human cell contains at least 1,000 mitochondria, each containing several copies of mitochondrial DNA. This DNA is tiny compared with the nuclear genome, and its structure and products have been fully elucidated. Whilst oxidative phosphorylation depends on the polypeptides encoded by mitochondrial DNA, it also requires a huge number of nuclear DNA products. Inherited deleterious mutations of mitochondrial DNA leading to inefficient oxidative phosphorylation have been described as 'mitochondrial disorders', with a variety of clinical presentations. When similar clinical presentations occur with no discernible mutation of mitochondrial DNA, histological and biochemical evidence is required for diagnosis. The number of these laboratory-proven inherited mitochondrial disorders is growing. It is also becoming clear that mitochondrial DNA defects can be acquired, the most common cause being therapy with highly active antiretroviral therapy (HAART) for human immunodeficiency virus-1 (HIV-1) infection. Whilst definitive diagnosis of inherited or acquired mitochrondrial dysfunction requires access to specialist laboratory techniques, routine laboratories have a role to play in the initial investigation and monitoring of these conditions.