ATP synthase F(1) complex subunit beta, mitochondrial

ATP synthase F(1) complex subunit beta (ATP5F1B) is the catalytic subunit of the mitochondrial F(1)F(0) ATP synthase complex (Complex V), which synthesizes ATP from ADP using the proton gradient generated by the electron transport chain (UniProt: P06576). It forms the catalytic core of the F(1) domain together with subunit alpha and couples ATP synthesis to proton translocation via a rotary mechanism involving the central stalk. Mutations in ATP5F1B are associated with hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2 (HUMOP2), characterized by failure to thrive and developmental delay.

ATP5F1B is relevant to Alzheimer's disease pathology, with Chaparral AD proteomics data showing consistent downregulation in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: −0.29). This reduction was observed in human brain samples analyzed by TMT-labeled proteomics across multiple subcellular fractions. The downregulation of this ATP synthase subunit suggests impaired mitochondrial energy production capacity in AD brain, consistent with documented mitochondrial dysfunction in Alzheimer's pathogenesis.