ATP synthase F(1) complex subunit alpha, mitochondrial

ATP synthase F(1) complex subunit alpha (ATP5F1A) is a catalytic subunit of the mitochondrial ATP synthase (Complex V), which synthesizes ATP from ADP using the proton gradient generated by the electron transport chain (UniProt: P25705). The protein forms part of the soluble F(1) head domain and works together with subunit beta to constitute the catalytic core; it also binds the bacterial siderophore enterobactin, facilitating mitochondrial iron accumulation (UniProt: P25705).

ATP5F1A is implicated in several monogenic mitochondrial disorders affecting energy metabolism, including combined oxidative phosphorylation deficiency 22 and mitochondrial complex V deficiency subtypes 4A and 4B, which present with neurologic symptoms ranging from encephalopathy to developmental delay and failure to thrive (UniProt: P25705).

In Alzheimer's disease, ATP5F1A shows down-regulation in post-mortem AD brain tissue relative to age-matched controls (mean log2FC −0.35; Chaparral AD proteomics), consistent with the bioenergetic dysfunction documented in AD neurodegeneration. This decreased expression may reflect impaired mitochondrial ATP production capacity in affected neurons.