ATP synthase F(1) complex subunit gamma, mitochondrial

ATP synthase F(1) complex subunit gamma (ATP5F1C) is a mitochondrial protein that forms part of the F(1) head domain of the ATP synthase complex, catalyzing ATP synthesis from ADP using the proton gradient generated by the respiratory chain (UniProt: P36542). The protein participates in the rotary mechanism coupling proton translocation to ATP synthesis in the mitochondrial membrane and is essential for F(1) assembly intermediate formation (UniProt: P36542).

ATP5F1C functions within the mitochondrial oxidative phosphorylation pathway, central to cellular energy metabolism. The protein is involved in ATP production across multiple subcellular compartments (UniProt: P36542).

In Alzheimer's Disease, ATP5F1C is significantly downregulated in post-mortem human brain tissue compared to age-matched controls (Chaparral AD proteomics). Analysis of TMT-labeled proteomics across four subcellular fractions revealed a mean log2 fold-change of −0.38, indicating reduced expression of this critical ATP synthase component in AD brain. This downregulation may reflect impaired mitochondrial oxidative phosphorylation capacity in Alzheimer's pathology.