FARS2 Human

The FARS2 gene is located on chromosome 6 and encodes the mitochondrial phenylalanyl-tRNA synthetase. This enzyme is part of the aminoacyl-tRNA synthetase family, which is responsible for charging tRNAs with their respective amino acids. The FARS2 protein is composed of several domains that facilitate its function, including a catalytic domain that binds ATP and phenylalanine, and an anticodon-binding domain that interacts with tRNA.

FARS2 is responsible for the aminoacylation of tRNA with phenylalanine, a process that is critical for mitochondrial protein synthesis. This enzyme ensures that phenylalanine is correctly incorporated into mitochondrial proteins, which are essential for the proper functioning of the mitochondrial respiratory chain. Additionally, FARS2 can catalyze the attachment of an oxidized form of phenylalanine, meta-tyrosine, to tRNA, which may play a role in the cellular response to oxidative stress .

Mutations in the FARS2 gene have been associated with several mitochondrial disorders. One such disorder is combined oxidative phosphorylation deficiency 14 (COXPD14), also known as Alpers encephalopathy. This condition is characterized by severe neurological symptoms, including developmental delay, seizures, and liver dysfunction. Another condition linked to FARS2 mutations is spastic paraplegia 77 (SPG77), an autosomal recessive disorder that leads to progressive weakness and stiffness of the legs .

Research on FARS2 has provided valuable insights into the mechanisms underlying mitochondrial diseases. Studies have shown that FARS2 deficiency can impair mitochondrial function, leading to reduced ATP production and increased oxidative stress. Animal models with FARS2 mutations have been used to study the pathogenesis of these disorders and to develop potential therapeutic strategies .