Calcium-binding mitochondrial carrier protein Aralar1

Calcium-binding mitochondrial carrier protein Aralar1 (also known as SLC25A12) is a protein that in humans is encoded by the SLC25A12 gene. It is a member of the mitochondrial carrier family and plays a crucial role in the malate-aspartate shuttle (MAS), a major system of electron transport in mitochondria.

Function[edit | edit source]

Aralar1 is a calcium-binding mitochondrial carrier protein involved in calcium homeostasis. It is primarily located in the inner mitochondrial membrane, where it facilitates the transport of glutamate across the membrane. This is essential for the functioning of the malate-aspartate shuttle, which transfers reducing equivalents from the cytosol to the mitochondria.

The protein is also involved in the regulation of calcium signaling, which is crucial for various cellular processes such as neuronal signaling, muscle contraction, and apoptosis. It has been suggested that Aralar1 may play a role in neurodevelopmental disorders, although further research is needed to confirm this.

Structure[edit | edit source]

Aralar1 is a multi-domain protein that contains three EF-hand domains, which are responsible for its calcium-binding properties. It also contains six transmembrane domains, which allow it to span the inner mitochondrial membrane.

Clinical significance[edit | edit source]

Mutations in the SLC25A12 gene have been associated with various neurodevelopmental disorders, including autism, global developmental delay, and hypotonia. These mutations can lead to a decrease in Aralar1 function, which can disrupt the malate-aspartate shuttle and lead to a buildup of glutamate in the mitochondria. This can cause mitochondrial dysfunction, which is thought to contribute to the pathogenesis of these disorders.