MT-ND4L

The MT-ND4L gene provides instructions for making a protein called NADH dehydrogenase 4L. This protein is part of a large enzyme complex known as complex I, which is active in mitochondria. 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.

Complex I is one of several enzyme complexes necessary for oxidative phosphorylation. Within mitochondria, these complexes are embedded in a tightly folded, specialized membrane called the inner mitochondrial membrane. During oxidative phosphorylation, mitochondrial enzyme complexes carry out chemical reactions that drive the production of ATP. Specifically, they create an unequal electrical charge on either side of the inner mitochondrial membrane through a step-by-step transfer of negatively charged particles called electrons. This difference in electrical charge provides the energy for ATP production.

Complex I is responsible for the first step in the electron transport process, the transfer of electrons from a molecule called NADH to another molecule called ubiquinone. Electrons are then passed from ubiquinone through several other enzyme complexes to provide energy for the generation of ATP.

Leber hereditary optic neuropathy - caused by mutations in the MT-ND4L gene

A mutation in the MT-ND4L gene has been identified in several families with Leber hereditary optic neuropathy. This mutation, which can be written as T10663C or Val65Ala, changes a single protein building block (amino acid) in the NADH dehydrogenase 4L protein. Specifically, it replaces the amino acid valine with the amino acid alanine at protein position 65.

Researchers have not determined how a mutation in the MT-ND4L gene can lead to the vision loss characteristic of Leber hereditary optic neuropathy. This genetic change appears to disrupt the normal activity of complex I in the mitochondrial inner membrane, which may affect the production of ATP. It remains unclear, however, why the effects of this mutation are limited to the nerve that relays visual information from the eye to the brain (the optic nerve). Additional genetic and environmental factors probably contribute to the features of Leber hereditary optic neuropathy.