Mitochondrial Disease
Mutations in Mitochondrial DNA Result in Severe Metabolic Disorders
Mitochondrial diseases, once thought to be relatively rare, have been found to be as prevalent in the US as Cystic Fibrosis. Mitochondrial diseases are caused by mutations in the mitochondrial DNA, and can be inherited, or can originate in the patient. Their severity and range of symptoms highlight the importance of maintianing mitochondrial function.
The Mitochondrion
The mitochondrion is an organelle, found within all human cells except red blood cells, and is responsible for generating the majority of the cell’s energy through a process called oxidative phosphorylation. The number of mitochondria per cell can range from dozens to hundreds, depending on the cell.
Mitochondrial DNA
The mitochondrion is a fascinating organelle, not only because it is the power plant of the cell and essential for much of metabolism, but also because it contains its own DNA - its own genome. The presence of the circular chromosome within mitochondria has led scientists to hypothesize that the mitochondrion originated when a bacteria-like organism invaded another cell approximately 1.8 billion years ago, took up residence in a symbiotic relationship, and never left.
The mitochondrial DNA encodes proteins involved in energy production. Mutations in the mitochondrial DNA can severely affect the ability of the mitochondria to function, resulting in an energy shortage. Mitochondrial dysfunction can lead to increased oxidative stress, resulting in additional cellular damage. Inheriting or acquiring a mutation in the mitochondrial DNA can result in disease.
Maternal Inheritance of Mitochondrial DNA
Mitochondria and mitochondrial DNA are inherited only from the mother. Because of this, maternal inheritance, or the passing of the disease from mother to child, is a hallmark of mitochondrial diseases. Mitochondrial disease can also be sporadic, meaning a mutation was not inherited, but occurred within the patient during early development.
Mitochondrial Disease Symptoms and Incidence
Mitochondrial diseases are characterized by a multitude of symptoms affecting many different organs, including muscle weakness, blindness, deafness, seizures, and cardiac symptoms. Diagnosis of mitochondrial disease is complicated by the fact that mutations usually are found in only a fraction of the mitochondrial genomes in a given cell. The severity and specific symptoms of mitochondrial disease depend on the proportion of damaged mitochondria, which can vary between people, between tissues, between cells, and can also change with age. If mitochondrial disease is suspected, biochemical tests for mitochondrial function and sequencing of the mitochondrial DNA can be used in diagnosis.
The incidence of mitochondrial diseases is an area of current research. According to the Cleveland Clinic, one in 4,000 children in the US will be diagnosed with a mitochondrial disease before they reach 10 years of age, which is similar to the incidence of Cystic Fibrosis in caucasian births in the US.
Mitochondrial DNA Mutations and Aging and Disease
There has been much interest in whether mutations in mitochondrial DNA can contribute to other conditions besides the classical mitochondrial diseases. Mitochondrial DNA does accumulate mutations with age, and it remains an intriguing question whether these mutations reach a level high enough to cause problems with mitochondrial energy production. Mutations in mitochondrial DNA may contribute to the loss of neurons in Alzheimer's and Parkinson's disease, and have been associated with diabetes and autism.
Treatment of Mitochondrial DIsease
Currently, there are no cures for mitochondrial disorders, and treatment is aimed at minimizing symptoms and slowing disease progression through dietary modification and vitamin or nutrient supplementation. Because of the individuality of each case, these modifications must be tailored to the patient with the help of a dietitian experienced in metabolic disorders.
