Mitochondrial respiratory Complex V (F1Fo ATP synthase) — subunits and F1 assembly; ATP5F1A/ATP5F1B/ATP5F1D/ATP5F1E/ATP5PO/ATP5MC3/ATP5MD + ATPAF2/TMEM70

Complex V, the F1Fo ATP synthase, is the terminal enzyme of oxidative phosphorylation: it uses the proton-motive force generated by the electron transport chain (Complexes I-IV) to drive the synthesis of ATP from ADP and inorganic phosphate. It is a rotary molecular motor with two coupled sectors. The membrane-embedded Fo sector — the c-ring (ATP5MC1/2/3), the a-subunit (mtDNA-encoded MT-ATP6) and small membrane subunits including DAPIT (ATP5MD) and 6.8PL — conducts protons and rotates the central stalk; the matrix-facing F1 sector is the catalytic head, an alpha3-beta3 hexamer (ATP5F1A/ATP5F1B) whose three catalytic nucleotide sites are turned through their conformational cycle by the rotating central stalk (gamma/ATP5F1C, delta/ATP5F1D, epsilon/ATP5F1E). The peripheral (stator) stalk, anchored at the top by OSCP (ATP5PO), holds the F1 head stationary against the rotor so that rotation is converted into ATP synthesis rather than futile spinning. Assembly is factor-dependent: ATPAF2 (ATP12) is a matrix chaperone that binds the F1 alpha subunit to build the alpha3-beta3 catalytic core, and TMEM70 promotes assembly and dimerisation of the whole complex. Inherited defects in the subunits or assembly factors cause mitochondrial complex V (ATP synthase) deficiency — commonly a neonatal encephalopathy with 3-methylglutaconic aciduria, lactic acidosis and cardiomyopathy.

MODULE:mitochondrial_complex_vDRAFTProtein Complexmodules/mitochondrial_complex_v.yaml
proton motive force-driven mitochondrial ATP synthesisGO:0042776 mitochondrial proton-transporting ATP synthase complex assemblyGO:0033615
GO:0042776
proton motive force-driven mitochondrial ATP synthesis
The module is grounded in proton motive force-driven mitochondrial ATP synthesis (GO:0042776) — the reaction catalysed by Complex V.
GO:0033615
mitochondrial proton-transporting ATP synthase complex assembly
The dedicated factors (ATPAF2, TMEM70) mediate mitochondrial proton-transporting ATP synthase complex assembly (GO:0033615).
Reactome:R-HSA-8949580
F1Fo ATP synthase dimerizes
The catalytic cycle and assembly follow the human Reactome ATP-synthase reactions R-HSA-164832 (ATP synthesis) and R-HSA-8949580 (F1Fo dimerisation).
file:human/ATP5F1A/ATP5F1A-ai-review.yaml
ATP5F1A gene review (human)
The F1 alpha catalytic subunit (UniProtKB:P25705, GO:0005524) matches the previously completed human ATP5F1A review (on main).
file:human/ATP5F1B/ATP5F1B-ai-review.yaml
ATP5F1B gene review (human)
The F1 beta catalytic subunit (UniProtKB:P06576, GO:0005524) matches the previously completed human ATP5F1B review (on main).
file:human/ATP5MC3/ATP5MC3-ai-review.yaml
ATP5MC3 gene review (human)
The Fo c-ring subunit (UniProtKB:P48201, GO:0015078) matches the previously completed human ATP5MC3 review (on main).
file:human/TMEM70/TMEM70-ai-review.yaml
TMEM70 gene review (human)
The ATP synthase assembly factor (UniProtKB:Q9BUB7, GO:0030674) matches the previously completed human TMEM70 review (on main).
file:human/ATP5F1D/ATP5F1D-ai-review.yaml
ATP5F1D gene review (human)
The F1 delta central-stalk subunit (UniProtKB:P30049, GO:0005198) matches the completed human ATP5F1D review.
file:human/ATP5F1E/ATP5F1E-ai-review.yaml
ATP5F1E gene review (human)
The F1 epsilon central-stalk subunit (UniProtKB:P56381, GO:0005198) matches the completed human ATP5F1E review.
file:human/ATP5PO/ATP5PO-ai-review.yaml
ATP5PO gene review (human)
The OSCP peripheral-stalk subunit (UniProtKB:P48047, GO:0005198) matches the completed human ATP5PO review.
file:human/ATP5MD/ATP5MD-ai-review.yaml
ATP5MD gene review (human)
The DAPIT Fo membrane subunit (UniProtKB:Q96IX5, GO:0005198) matches the completed human ATP5MD review.
file:human/ATPAF2/ATPAF2-ai-review.yaml
ATPAF2 gene review (human)
The F1 assembly chaperone (UniProtKB:Q8N5M1, GO:0044183) matches the completed human ATPAF2 review.
4Nodes
3Parts
0Variant Sets
0Variants
9Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:mitochondrial_complex_v deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (9/9 grounded genes reviewed)

8 complete review(s) · 4 with deep research · 0 missing review · 5 reviewed but lacking deep research

Gene Review Complete Deep research
ATP5F1A P25705 ✓ ✓ ✓
ATP5F1B P06576 ✓ 86/89 ✓
ATP5F1D P30049 ✓ ✓ ✗
ATP5F1E P56381 ✓ ✓ ✗
ATP5MC3 P48201 ✓ ✓ ✓
ATP5MD Q96IX5 ✓ ✓ ✗
ATP5PO P48047 ✓ ✓ ✗
ATPAF2 Q8N5M1 ✓ ✓ ✗
TMEM70 Q9BUB7 ✓ ✓ ✓

Details

Context
mitochondrial inner membraneGO:0005743 mitochondrial matrixGO:0005759
Mitochondrial respiratory Complex V (F1Fo ATP synthase)Protein Complexmitochondrial_complex_v
proton motive force-driven mitochondrial ATP synthesisGO:0042776 mitochondrial proton-transporting ATP synthase complex assemblyGO:0033615
Context
mitochondrial inner membraneGO:0005743 mitochondrial matrixGO:0005759

Mitochondrial respiratory Complex V (F1Fo ATP synthase), grounded to the human subunits ATP5F1A (UniProtKB:P25705), ATP5F1B (P06576), ATP5F1D (P30049), ATP5F1E (P56381), ATP5PO (P48047), ATP5MC3 (P48201), ATP5MD/DAPIT (Q96IX5) and the assembly factors ATPAF2 (Q8N5M1, GO:0044183) and TMEM70 (Q9BUB7). GO molecular-function/BP/location terms were taken from the completed human gene reviews and verified against the local go.db; Reactome reaction ids/titles were verified against the local reactome cache. The complex is modelled as F1 (catalytic head + central stalk) and Fo (membrane/proton-conducting) PROTEIN_COMPLEX nodes plus an assembly node; the catalytic activity (GO:0046933) is carried by the alpha/beta subunits, while the central-stalk/OSCP/DAPIT subunits are structural (GO:0005198). The a-subunit (MT-ATP6/MT-ATP8) and additional peripheral-stalk subunits (ATP5PB/PD/PF, ATP5ME/MF/MG) are mtDNA-encoded or reviewed elsewhere; the current ATP synthase complex term is GO:0045259 (proton-transporting ATP synthase complex). Complex V is driven by the proton gradient built by Complexes I-IV (oxphos.yaml, Complex III and Complex IV modules). Disorders: mitochondrial complex V (ATP synthase) deficiency nuclear types 1-9 — typically neonatal encephalopathy with 3-methylglutaconic aciduria, lactic acidosis and cardiomyopathy (ATPAF2 = MC5DN1, TMEM70 = MC5DN2 the commonest, ATP5F1E = MC5DN3, ATP5F1D = MC5DN5). NOTE: the ATP5MD folder was initially mis-fetched as Q9UI09 (NDUFA12, Complex I) and re-fetched with the correct DAPIT accession Q96IX5.

Connections

complex_v_assembly -> complex_v_f1 Positively Regulates
ATPAF2 builds the F1 alpha3-beta3 catalytic core and TMEM70 promotes assembly/dimerisation of the holoenzyme.
complex_v_fo -> complex_v_f1 Provides Input For
Proton conduction through the Fo c-ring rotates the central stalk, driving ATP synthesis at the F1 catalytic head.
Part 1: F1 catalytic head and central stalk (ATP synthesis)
F1 sector (alpha3-beta3 catalytic head + central stalk)Protein Complexcomplex_v_f1

Annotons

ATP5F1A: F1 alpha subunit
atp5f1a_activity
Participant: Family: ATP synthase alpha subunit family (ATP5F1A)
Family:
ATP synthase alpha subunit family (ATP5F1A)PANTHER:PTHR48082
Representative Members: ATP5F1A (human)UniProtKB:P25705

Function

proton-transporting ATP synthase activity, rotational mechanismGO:0046933
Substrates: ADP phosphate
Products: ATP

Locations

mitochondrial inner membraneGO:0005743

F1 alpha subunit of the catalytic head.

ATP5F1B: F1 beta subunit (catalytic)
atp5f1b_activity
Participant: Family: ATP synthase beta subunit family (ATP5F1B)
Family:
ATP synthase beta subunit family (ATP5F1B)PANTHER:PTHR15184
Representative Members: ATP5F1B (human)UniProtKB:P06576

Function

proton-transporting ATP synthase activity, rotational mechanismGO:0046933
Substrates: ADP phosphate
Products: ATP

Locations

mitochondrial inner membraneGO:0005743

F1 beta subunit; carries the catalytic nucleotide sites.

ATP5F1D: F1 delta subunit (central stalk)
atp5f1d_activity
Participant: Family: ATP synthase delta/epsilon central-stalk family (ATP5F1D)
Family:
ATP synthase delta/epsilon central-stalk family (ATP5F1D)PANTHER:PTHR13822
Representative Members: ATP5F1D (human)UniProtKB:P30049

Function

structural molecule activityGO:0005198
Substrates: (central-stalk coupling)
Products: rotation transmitted to the F1 catalytic sites

Locations

mitochondrial inner membraneGO:0005743

Central-stalk delta subunit.

ATP5F1E: F1 epsilon subunit (central stalk)
atp5f1e_activity
Participant: Family: ATP synthase epsilon central-stalk family (ATP5F1E)
Family:
ATP synthase epsilon central-stalk family (ATP5F1E)PANTHER:PTHR12448
Representative Members: ATP5F1E (human)UniProtKB:P56381

Function

structural molecule activityGO:0005198
Substrates: (central-stalk coupling)
Products: rotation transmitted to the F1 catalytic sites

Locations

mitochondrial inner membraneGO:0005743

Central-stalk epsilon subunit.

ATP5PO: OSCP peripheral-stalk subunit
atp5po_activity
Participant: Family: ATP synthase OSCP/delta(bacterial) family (ATP5PO)
Family:
ATP synthase OSCP/delta(bacterial) family (ATP5PO)PANTHER:PTHR11910
Representative Members: ATP5PO (human)UniProtKB:P48047

Function

structural molecule activityGO:0005198
Substrates: (stator anchoring of the F1 head)
Products: productive coupling (oligomycin-sensitive ATP synthesis)

Locations

mitochondrial inner membraneGO:0005743

OSCP; anchors the F1 head to the peripheral stalk.

Part 2: Fo membrane sector (proton conduction)
Fo sector (c-ring and small membrane subunits)Protein Complexcomplex_v_fo

Annotons

ATP5MC3: Fo c-ring subunit
atp5mc3_activity
Participant: Family: ATP synthase c-subunit family (ATP5MC)
Family:
ATP synthase c-subunit family (ATP5MC)PANTHER:PTHR10031
Representative Members: ATP5MC3 (human)UniProtKB:P48201

Function

proton transmembrane transporter activityGO:0015078
Substrates: H+ (intermembrane space)
Products: H+ (matrix), rotor rotation

Locations

mitochondrial inner membraneGO:0005743

c-ring subunit; proton-driven rotor.

ATP5MD (DAPIT): Fo membrane subunit
atp5md_activity
Participant: Family: ATP synthase DAPIT/subunit-k family (ATP5MD)
Family:
ATP synthase DAPIT/subunit-k family (ATP5MD)PANTHER:PTHR34038
Representative Members: ATP5MD (human)UniProtKB:Q96IX5

Function

structural molecule activityGO:0005198
Substrates: (Fo membrane scaffold)
Products: stable/dimerised ATP synthase

Locations

mitochondrial inner membraneGO:0005743

Small Fo membrane subunit (stability/dimerisation).

Part 3: F1/holoenzyme assembly factors
ATP synthase assembly (F1 chaperone and dimerisation)Reactioncomplex_v_assembly

Annotons

ATPAF2 (ATP12): F1 assembly chaperone
atpaf2_activity
Participant: Family: ATP12/ATPAF2 assembly-factor family
Family:
ATP12/ATPAF2 assembly-factor familyPANTHER:PTHR21013
Representative Members: ATPAF2 (human)UniProtKB:Q8N5M1

Function

protein folding chaperoneGO:0044183
Substrates: unassembled F1 alpha subunit (ATP5F1A)
Products: alpha3-beta3 catalytic core

Locations

mitochondrial matrixGO:0005759

F1 alpha-subunit assembly chaperone.

TMEM70: ATP synthase assembly/dimerisation factor
tmem70_activity
Participant: Family: TMEM70 assembly-factor family
Family:
TMEM70 assembly-factor familyPANTHER:PTHR13281
Representative Members: TMEM70 (human)UniProtKB:Q9BUB7

Processes

mitochondrial proton-transporting ATP synthase complex assemblyGO:0033615

Locations

mitochondrial inner membraneGO:0005743

Promotes ATP synthase assembly and dimerisation.

Reactome:R-HSA-8949580
F1Fo ATP synthase dimerizes (human Reactome reaction)
file:human/TMEM70/TMEM70-ai-review.yaml
inner-membrane assembly factor promoting ATP synthase biogenesis/dimerisation; deficiency = MC5DN2 (commonest nuclear complex V defect)