MT-ATP6

The MT-ATP6 gene provides information for making a protein that is essential for normal mitochondrial function. Mitochondria are structures within cells that convert the energy from food into a form that cells can use. These cellular structures produce energy through a process called oxidative phosphorylation, which uses oxygen and simple sugars to create adenosine triphosphate (ATP), the cell's main energy source.

The MT-ATP6 protein forms one part (subunit) of a large enzyme called ATP synthase. This enzyme, which is also known as complex V, is responsible for the final step of oxidative phosphorylation. Specifically, one segment of ATP synthase allows positively charged particles, called protons, to flow across a specialized membrane inside mitochondria. Another segment of the enzyme uses the energy created by this proton flow to convert a molecule called adenosine diphosphate (ADP) to ATP.

neuropathy, ataxia, and retinitis pigmentosa - caused by mutations in the MT-ATP6 gene

A small number of mutations in the MT-ATP6 gene have been identified in people with neuropathy, ataxia, and retinitis pigmentosa (NARP). Each of these mutations changes one DNA building block (nucleotide) in the MT-ATP6 gene. The most common genetic change replaces the nucleotide thymine with the nucleotide cytosine at position 8993 (written as T8993C). The mutations that cause NARP alter the structure or function of ATP synthase, reducing the ability of mitochondria to produce ATP. The precise effects of these mutations are unclear, however. Researchers continue to investigate how changes in the MT-ATP6 gene interfere with ATP production and lead to muscle weakness, vision loss, and the other features of NARP.

other disorders - caused by mutations in the MT-ATP6 gene

Some of the mutations that cause NARP are also responsible for a similar, but more severe, condition called Leigh syndrome. This condition is a progressive brain disorder that usually appears in infancy or early childhood. Affected children may experience vomiting, seizures, delayed development, muscle weakness, and problems with movement. Heart disease, kidney problems, and difficulty breathing can also occur in people with this disorder.

Most of the body's cells contain thousands of mitochondria, each with one or more copies of mitochondrial DNA. The severity of some mitochondrial disorders is associated with the percentage of mitochondria in each cell that has a particular genetic change. People with maternally inherited Leigh syndrome tend to have a very high percentage of mitochondria with an MT-ATP6 mutation (greater than 90 percent to 95 percent). The less-severe features of NARP result from a lower percentage of mitochondria with the mutation, typically 70 percent to 90 percent. Because these two conditions result from the same genetic change and can occur in different members of a single family, researchers believe that they may represent a spectrum of overlapping features instead of two distinct syndromes.

A condition called familial bilateral striatal necrosis, which is similar to Leigh syndrome, also results from changes in the MT-ATP6 gene. In the few reported cases with these mutations, affected children have had delayed development, problems with movement and coordination, weak muscle tone (hypotonia), and an unusually small head size (microcephaly). Researchers have not determined why MT-ATP6 mutations result in this combination of signs and symptoms in children with bilateral striatal necrosis.