NADH:Ubiquinone Oxidoreductase Subunit S4 (NDUFS4) mRNA (NDUFS4 mRNA)

NDUFS4 mRNA encodes the NADH:Ubiquinone Oxidoreductase Subunit S4, a critical accessory subunit required for the assembly and stability of Mitochondrial Complex I (UniProt: O43181). Complex I is the first and largest enzyme of the mitochondrial respiratory chain, responsible for transferring electrons from NADH to ubiquinone and generating the proton gradient necessary for ATP synthesis (PubMed: 22522445). Mutations in the NDUFS4 gene lead to the loss of this subunit, resulting in the instability of Complex I and severe energy failure in tissues with high metabolic demand. This deficiency is a primary cause of Leigh Syndrome, a progressive and fatal neurodegenerative disorder characterized by psychomotor regression and brainstem lesions (NIH: GARD). As a therapeutic target, NDUFS4 mRNA is utilized in mRNA replacement therapies, where exogenous mRNA is delivered to cells to restore the production of functional NDUFS4 protein. Current drug development efforts, such as Moderna's mRNA-3905, focus on using lipid nanoparticle-encapsulated mRNA to treat patients with NDUFS4-related mitochondrial deficiencies (Moderna Pipeline, 2024). This approach aims to rescue mitochondrial function and halt disease progression by providing a functional template for protein synthesis.

Other names

CI-18 kDa mRNAComplex I-18 kDa subunit mRNANADH dehydrogenase [ubiquinone] iron-sulfur protein 4 mRNACI-AQDQ mRNA

mRNA replacement therapy to restore functional NDUFS4 protein expression and mitochondrial Complex I assembly.