Serac1, or serine active site-containing protein 1, is a crucial component of the mitochondrial serine transporter complex. It localizes to the outer mitochondrial membrane and is part of the one-carbon cycle [1]. By interacting with the mitochondrial serine transporter protein SFXN1, Serac1 facilitates serine transport from the cytosol to the mitochondria, which is important for mitochondrial function and the maintenance of 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 [1]. Loss of Serac1 in these mice impairs the one-carbon cycle, disrupts the nucleotide pool balance, leading to primary mtDNA depletion due to insufficient nucleotide supply in mice, HEK293T cells, and patient-derived immortalized lymphocyte cells [1].

In conclusion, Serac1 is essential for mitochondrial function through its role in serine transport and the one-carbon cycle. The Serac1 KO mouse model has revealed its significance in maintaining mtDNA, providing insights into the molecular mechanisms underlying MEGD(H)EL syndrome, a disease associated with Serac1 deficiency [1].