Serac1, or serine active site-containing protein 1, localizes to the outer mitochondrial membrane and is a component of the mitochondrial serine transporter complex. It is crucial for the one-carbon cycle, as it interacts with the mitochondrial serine transporter protein SFXN1 to facilitate serine transport from the cytosol to the mitochondria. This process is essential for maintaining the balance of the nucleotide pool and mitochondrial DNA (mtDNA) [1].

Serac1-/-mice, a gene knockout (KO) mouse model, mimic the major diagnostic clinical and biochemical phenotypes of the mitochondrial 3-methylglutaconic aciduria with deafness, (hepatopathy), encephalopathy, and Leigh-like disease [MEGD(H)EL] syndrome. Loss of Serac1 in these mice, HEK293T cells, and patient-derived immortalized lymphocyte cells impairs the one-carbon cycle, disrupts the nucleotide pool balance, and leads to primary mtDNA depletion due to insufficient nucleotide supply. Nucleoside/nucleotide supplementation in vitro and in vivo can restore mtDNA content and mitochondrial function [1].

In conclusion, Serac1 is essential for mitochondrial function, specifically in maintaining mtDNA through its role in the one-carbon cycle and serine transport. The Serac1 KO mouse model has been instrumental in revealing its role in MEGD(H)EL syndrome, suggesting that nucleotide supplementation could be an effective therapeutic strategy for this syndrome [1].