Abstract 2536 Instability of the B12 trafficking chaperone MMADHC is mitochondrially regulated

MMADHC is a chaperone in the B12 trafficking pathway whose function is incompletely understood. Mutations in MMADHC lead to combined or isolated methylmalonic aciduria and/or homocystinuria aciduria due to its role in the cytoplasmic and mitochondrial branches, respectively of the B12 trafficking pathway. The first third of the MMADHC protein is predicted to be disordered while the last two-thirds is stably folded and belongs to the ferrodoxin nitroreductase superfamily and binds B12. Previous biochemical studies in our laboratory have demonstrated that MMADHC can load the B12 cofactor onto the cytoplasmic target, i.e.