Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial

MCCC1 encodes the alpha subunit of methylcrotonoyl-CoA carboxylase (MCCase), a biotin-dependent mitochondrial enzyme that catalyzes the conversion of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA during leucine and isovaleric acid catabolism (UniProt: Q96RQ3). The protein functions as part of a heteromeric complex essential for branched-chain amino acid metabolism.

Mutations in MCCC1 cause 3-methylcrotonoyl-CoA carboxylase 1 deficiency (MCC1D), an autosomal recessive disorder of leucine catabolism characterized by neurological involvement and organic aciduria (UniProt: Q96RQ3). The disease phenotype ranges from severe neonatal presentation to asymptomatic adult forms, often accompanied by secondary carnitine deficiency.

MCCC1 is upregulated in Alzheimer's disease brain tissue relative to age-matched controls (mean log2FC = 0.41; Chaparral AD proteomics). This elevation was detected in human post-mortem AD brain via TMT-labeled proteomics across subcellular fractions, suggesting altered branched-chain amino acid metabolism or mitochondrial function may be associated with AD pathology.