Surfeit locus protein 1

SURF1 (Surfeit locus protein 1) is a 300-amino-acid mitochondrial protein that functions as a component of the MITRAC complex, which regulates assembly of cytochrome c oxidase and the mitochondrial respiratory chain (UniProt: Q15526). The protein is essential for oxidative phosphorylation; pathogenic variants cause Mitochondrial complex IV deficiency, nuclear type 1 (MC4DN1), an autosomal recessive disorder presenting with early-onset encephalopathy, neurodegeneration, and progressive loss of motor and cognitive function. SURF1 mutations also underlie Charcot-Marie-Tooth disease, demyelinating type 4K (CMT4K), characterized by peripheral nerve demyelination and progressive weakness (UniProt: Q15526).

In Alzheimer's disease, SURF1 is significantly downregulated in post-mortem AD brain tissue relative to age-matched controls (mean log2 fold-change −0.3752, Chaparral AD proteomics). The downregulation was observed in a TMT-labeled quantitative proteomics study of four subcellular fractions from human brain tissue. This reduction may reflect impaired mitochondrial bioenergetics and oxidative phosphorylation capacity, processes increasingly recognized as dysfunctional in AD neurodegeneration.