protein
ATP synthase F(1) complex subunit alpha, mitochondrial
Gene
ATP5F1A
Organism
Homo sapiens(9606)
Length
553 aa
Mass
59,751 Da
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.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.349
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.3492 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Subunit alpha, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (Probable). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). With the catalytic subunit beta (ATP5F1B), forms the catalytic core in the F(1) domain (PubMed:37244256). Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (Probable). Binds the bacterial siderophore enterobactin and can promote mitochondrial accumulation of enterobactin-derived iron ions (PubMed:30146159)
Disease associations
Combined oxidative phosphorylation deficiency 22COXPD22
A mitochondrial disorder characterized by intrauterine growth retardation, microcephaly, hypotonia, pulmonary hypertension, failure to thrive, encephalopathy, and heart failure.
Mitochondrial complex V deficiency, nuclear type 4AMC5DN4A
An autosomal dominant mitochondrial disorder characterized by failure to thrive, feeding difficulties, hyperlactatemia, hyperammonemia, and increased serum alanine levels. Some affected individuals show spontaneous resolution of the symptoms in early childhood and have subsequent normal growth and development, whereas others show developmental delay with impaired intellectual development and movement abnormalities, including dystonia, ataxia, or spasticity.
Mitochondrial complex V deficiency, nuclear type 4BMC5DN4B
An autosomal recessive mitochondrial disorder characterized by severe neonatal encephalopathy resulting in death in the first weeks of life. Affected individuals do not show dysmorphic features or organomegaly, and manifest neurologic features such as irritability, a high-pitched cry, a horizontal and vertical nystagmus, abnormal primitive reflexes, and tonus dysregulation. Post-mortem anatomopathological examination shows extensive cerebral damage, hypoplastic lungs, and renal and skeletal lesions.
Sources
Last updated 5/8/2026, 6:27:42 AM