solute carrier family 25 member 4
The SLC25A4 gene provides the instructions for making a protein called adenine nucleotide translocase type 1 (ANT1). ANT1 functions in mitochondria, which are structures within cells that convert the energy from food into a form that cells can use. This process, called oxidative phosphorylation, converts adenosine diphosphate (ADP) into adenosine triphosphate (ATP), the cell's main energy source. ANT1 forms a channel in the inner membrane of mitochondria. This channel allows ADP into mitochondria and ATP out of mitochondria to be used as energy for the cell. ANT1 may also be a part of another structure in the inner membrane called the mitochondrial permeability transition pore. This structure allows various molecules to pass into mitochondria and is thought to play a role in the self-destruction (apoptosis) of the cell.
At least five mutations in the SLC25A4 gene have been reported to cause an eye condition called progressive external ophthalmoplegia. This disorder weakens the muscles that control eye movement and causes the eyelids to droop (ptosis). When caused by SLC25A4 gene mutations, progressive external ophthalmoplegia is inherited in an autosomal dominant pattern, which means one copy of the gene in each cell is mutated. These mutations impair the movement of ADP and ATP into and out of mitochondria; however, it is not well understood what role these changes play in the cause of the condition.
Mitochondria each contain a small amount of DNA, known as mitochondrial DNA (mtDNA), which is essential for the normal function of these structures. Although the mechanism is unclear, mutations in the SLC25A4 gene result in large deletions of genetic material from mtDNA in muscle tissue. Researchers have not determined how deletions of mtDNA lead to the specific signs and symptoms of progressive external ophthalmoplegia, although the features of the condition are probably related to impaired oxidative phosphorylation. It has been suggested that eye muscles are commonly affected by mitochondrial defects because they are especially dependent on oxidative phosphorylation for energy.
Mutations in the SLC25A4 gene can also cause a disorder characterized by myopathy and hypertrophic cardiomyopathy. Myopathy is weakness of the muscles used for movement, and cardiomyopathy is a thickening of the heart muscle that forces the heart to work harder to pump blood. This disorder is inherited in an autosomal recessive pattern, which means both copies of the SLC25A4 gene in each cell are mutated. The mutations associated with this disorder prevent production of ANT1 channels. As in progressive external ophthalmoplegia (described above), the mutations result in deletions of mtDNA, although the mechanism is unclear. Researchers are unsure how deletions of mtDNA lead to myopathy and hypertrophic cardiomyopathy.