Mitochondrial respiratory Complex I core (NADH:ubiquinone oxidoreductase) — catalytic N and Q modules; NDUFV1/NDUFV2/NDUFS1-3/NDUFS6-8/NDUFA9

Respiratory Complex I (NADH:ubiquinone oxidoreductase) is the largest enzyme of the electron transport chain and its main entry point: it oxidises NADH, passes the electrons through a chain of flavin and iron-sulfur cofactors to reduce ubiquinone, and uses the energy released to pump four protons across the inner membrane. This module covers the catalytic core of the L-shaped peripheral (matrix) arm — the seven conserved "core" nuclear subunits plus the closely associated flavoprotein subunits — organised into two functional modules. The N-module (NADH-oxidising) holds the flavin site: NDUFV1 (51 kDa) binds FMN and the NADH substrate, NDUFV2 (24 kDa) carries the first [2Fe-2S] cluster (N1a), and NDUFS1 (75 kDa) provides further Fe-S clusters, forming the flavoprotein (FP) subcomplex with the accessory NDUFS6. The Q-module (ubiquinone-reducing) forms the wire to the quinone site: NDUFS2 (49 kDa) and NDUFS3 (30 kDa) are cofactor-less core subunits shaping the ubiquinone cavity, NDUFS7 (PSST) coordinates the terminal [4Fe-4S] cluster N2 that donates electrons to ubiquinone, NDUFS8 (TYKY) carries the N6a/N6b [4Fe-4S] clusters of the electron-transfer wire, and the accessory NDUFA9 (SDR-fold, structural NADPH) stabilises the Q-module/membrane-arm junction; NDUFS4 is an accessory subunit required for assembly and stability of the whole peripheral arm. Inherited defects in these core subunits are among the commonest causes of mitochondrial complex I deficiency — typically Leigh syndrome, leukoencephalopathy, fatal infantile lactic acidosis or encephalocardiomyopathy.

MODULE:mitochondrial_complex_i_coreDRAFTProtein Complexmodules/mitochondrial_complex_i_core.yaml
mitochondrial electron transport, NADH to ubiquinoneGO:0006120 mitochondrial respiratory chain complex I assemblyGO:0032981
GO:0006120
mitochondrial electron transport, NADH to ubiquinone
The module is grounded in mitochondrial electron transport, NADH to ubiquinone (GO:0006120) — the reaction catalysed by Complex I.
GO:0032981
mitochondrial respiratory chain complex I assembly
The core subunits define the catalytic peripheral arm whose assembly is mitochondrial respiratory chain complex I assembly (GO:0032981).
Reactome:R-HSA-163217
Complex I oxidises NADH to NAD+, reduces CoQ to CoQH2
The catalytic reaction follows the human Reactome "Complex I oxidises NADH to NAD+, reduces CoQ to CoQH2" reaction (R-HSA-163217).
file:human/NDUFV1/NDUFV1-ai-review.yaml
NDUFV1 gene review (human)
The FMN/NADH catalytic subunit (UniProtKB:P49821, GO:0003954) matches the previously completed human NDUFV1 review (on main).
file:human/NDUFS1/NDUFS1-ai-review.yaml
NDUFS1 gene review (human)
The 75 kDa Fe-S electron-transfer subunit (UniProtKB:P28331, GO:0009055) matches the previously completed human NDUFS1 review (on main).
file:human/NDUFS2/NDUFS2-ai-review.yaml
NDUFS2 gene review (human)
The 49 kDa Q-module core subunit (UniProtKB:O75306, GO:0048039) matches the previously completed human NDUFS2 review (on main).
file:human/NDUFS4/NDUFS4-ai-review.yaml
NDUFS4 gene review (human)
The NDUFS4 accessory/assembly subunit (UniProtKB:O43181) matches the previously completed human NDUFS4 review (on main).
file:human/NDUFV2/NDUFV2-ai-review.yaml
NDUFV2 gene review (human)
The 24 kDa N1a [2Fe-2S] N-module subunit (UniProtKB:P19404, GO:0008137) matches the completed human NDUFV2 review.
file:human/NDUFS3/NDUFS3-ai-review.yaml
NDUFS3 gene review (human)
The 30 kDa Q-module core subunit (UniProtKB:O75489, GO:0005198) matches the completed human NDUFS3 review.
file:human/NDUFS6/NDUFS6-ai-review.yaml
NDUFS6 gene review (human)
The 13 kDa zinc-binding N-module accessory subunit (UniProtKB:O75380, GO:0005198) matches the completed human NDUFS6 review.
file:human/NDUFS7/NDUFS7-ai-review.yaml
NDUFS7 gene review (human)
The PSST subunit coordinating the N2 [4Fe-4S] cluster (UniProtKB:O75251, GO:0008137/GO:0051539) matches the completed human NDUFS7 review.
file:human/NDUFS8/NDUFS8-ai-review.yaml
NDUFS8 gene review (human)
The TYKY subunit coordinating the N6a/N6b [4Fe-4S] clusters (UniProtKB:O00217, GO:0051539) matches the completed human NDUFS8 review.
file:human/NDUFA9/NDUFA9-ai-review.yaml
NDUFA9 gene review (human)
The 39 kDa SDR-fold Q-module/junction accessory subunit (UniProtKB:Q16795, GO:0005198) matches the completed human NDUFA9 review.
4Nodes
3Parts
0Variant Sets
0Variants
10Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:mitochondrial_complex_i_core 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 (10/10 grounded genes reviewed)

10 complete review(s) · 4 with deep research · 0 missing review · 6 reviewed but lacking deep research

Gene Review Complete Deep research
NDUFA9 Q16795 ✓ ✓ ✗
NDUFS1 P28331 ✓ ✓ ✓
NDUFS2 O75306 ✓ ✓ ✓
NDUFS3 O75489 ✓ ✓ ✗
NDUFS4 O43181 ✓ ✓ ✓
NDUFS6 O75380 ✓ ✓ ✗
NDUFS7 O75251 ✓ ✓ ✗
NDUFS8 O00217 ✓ ✓ ✗
NDUFV1 P49821 ✓ ✓ ✓
NDUFV2 P19404 ✓ ✓ ✗

Details

Context
mitochondrial inner membraneGO:0005743
Mitochondrial respiratory Complex I core (N and Q modules)Protein Complexmitochondrial_complex_i_core
mitochondrial electron transport, NADH to ubiquinoneGO:0006120 mitochondrial respiratory chain complex I assemblyGO:0032981
Context
mitochondrial inner membraneGO:0005743

Catalytic core of mitochondrial respiratory Complex I (NADH:ubiquinone oxidoreductase), grounded to the human N-module subunits NDUFV1 (UniProtKB:P49821, GO:0003954), NDUFV2 (P19404, GO:0008137), NDUFS1 (P28331, GO:0009055) and accessory NDUFS6 (O75380, GO:0005198); the Q-module subunits NDUFS2 (O75306, GO:0048039), NDUFS3 (O75489, GO:0005198), NDUFS7 (O75251, GO:0008137 + N2 [4Fe-4S]), NDUFS8 (O00217, GO:0051539) and accessory NDUFA9 (Q16795, GO:0005198); and the peripheral-arm assembly subunit NDUFS4 (O43181). GO molecular-function/BP/location terms were taken from the completed human gene reviews and verified against the local go.db; the catalytic reaction (R-HSA-163217) was verified against the local reactome cache. The complex is modelled as N-module and Q-module PROTEIN_COMPLEX nodes plus an assembly-accessory node; only the cofactor-bearing subunits carry redox/catalytic MFs (NDUFV1 FMN/NADH, NDUFV2/NDUFS7 Fe-S/NADH dehydrogenase, NDUFS8 [4Fe-4S], NDUFS1 electron transfer, NDUFS2 quinone binding), while the cofactor-less core (NDUFS3) and accessory subunits (NDUFS6, NDUFA9, NDUFS4) are structural. The full holo-Complex I additionally has ~30 more accessory subunits and the mtDNA-encoded membrane-arm ND subunits (MT-ND1-6/4L), plus dedicated assembly factors (NDUFAF1-8, etc.) — a further module. The current Complex I membership term is GO:0045271 (GO:0005747 obsolete); Complex I feeds electrons to ubiquinone shared with Complex II, then to Complex III (bc1) → cytochrome c → Complex IV. Disorders: mitochondrial complex I deficiency (the commonest OXPHOS defect) — Leigh syndrome (NDUFS4/S7/S8, NDUFV1), leukoencephalopathy, fatal infantile lactic acidosis (NDUFS6), encephalocardiomyopathy (NDUFV2) and others.

Connections

complex_i_n_module -> complex_i_q_module Provides Input For
Electrons from NADH oxidation at the FMN/N-module are relayed through the Fe-S wire to the Q-module N2 cluster, which reduces ubiquinone.
complex_i_ndufs4 -> complex_i_n_module Positively Regulates
NDUFS4 is required for assembly and stability of the catalytic peripheral arm.
Part 1: N-module (NADH oxidation, FMN + entry Fe-S clusters)
N-module (flavoprotein / NADH-oxidising)Protein Complexcomplex_i_n_module

Annotons

NDUFV1: FMN/NADH catalytic subunit (51 kDa)
ndufv1_activity
Participant: Family: NADH dehydrogenase flavoprotein 1 family (NDUFV1)
Family:
NADH dehydrogenase flavoprotein 1 family (NDUFV1)PANTHER:PTHR11780
Representative Members: NDUFV1 (human)UniProtKB:P49821

Function

NADH dehydrogenase activityGO:0003954
Substrates: NADH FMN
Products: NAD+ reduced FMN (electrons to the Fe-S wire)

Locations

mitochondrial inner membraneGO:0005743

FMN-containing NADH-oxidising catalytic subunit.

NDUFV2: N1a [2Fe-2S] subunit (24 kDa)
ndufv2_activity
Participant: Family: NADH dehydrogenase flavoprotein 2 family (NDUFV2)
Family:
NADH dehydrogenase flavoprotein 2 family (NDUFV2)PANTHER:PTHR10371
Representative Members: NDUFV2 (human)UniProtKB:P19404

Function

electron transfer activityGO:0009055
Substrates: electrons from FMN
Products: electrons transferred via the N1a [2Fe-2S] cluster

Locations

mitochondrial inner membraneGO:0005743

Carries the N1a [2Fe-2S] cluster.

NDUFS1: 75 kDa Fe-S subunit
ndufs1_activity
Participant: Family: NADH-quinone oxidoreductase G/NDUFS1 family
Family:
NADH-quinone oxidoreductase G/NDUFS1 familyPANTHER:PTHR43105
Representative Members: NDUFS1 (human)UniProtKB:P28331

Function

electron transfer activityGO:0009055
Substrates: electrons from the FMN/N1a site
Products: electrons relayed through its Fe-S clusters toward the Q-module

Locations

mitochondrial inner membraneGO:0005743

75 kDa Fe-S electron-transfer subunit.

NDUFS6: zinc-binding N-module accessory (13 kDa)
ndufs6_activity
Participant: Family: NDUFS6 accessory-subunit family
Family:
NDUFS6 accessory-subunit familyPANTHER:PTHR13156
Representative Members: NDUFS6 (human)UniProtKB:O75380

Function

structural molecule activityGO:0005198
Substrates: (N-module stabilisation)
Products: assembled/stable N-module

Locations

mitochondrial inner membraneGO:0005743

Accessory subunit stabilising the N-module.

Part 2: Q-module (ubiquinone reduction, terminal Fe-S wire)
Q-module (ubiquinone-reducing)Protein Complexcomplex_i_q_module

Annotons

NDUFS2: 49 kDa Q-module core subunit
ndufs2_activity
Participant: Family: NADH-quinone oxidoreductase D/NDUFS2 family
Family:
NADH-quinone oxidoreductase D/NDUFS2 familyPANTHER:PTHR11993
Representative Members: NDUFS2 (human)UniProtKB:O75306

Function

ubiquinone bindingGO:0048039
Substrates: ubiquinone
Products: ubiquinol (reduced at the Q site)

Locations

mitochondrial inner membraneGO:0005743

49 kDa core subunit at the ubiquinone site.

NDUFS3: 30 kDa Q-module core subunit
ndufs3_activity
Participant: Family: NADH-quinone oxidoreductase C/NDUFS3 family
Family:
NADH-quinone oxidoreductase C/NDUFS3 familyPANTHER:PTHR10884
Representative Members: NDUFS3 (human)UniProtKB:O75489

Function

structural molecule activityGO:0005198
Substrates: (Q-module core scaffold)
Products: assembled/stable Q-module

Locations

mitochondrial inner membraneGO:0005743

30 kDa core structural subunit of the Q-module.

NDUFS7 (PSST): N2 [4Fe-4S] subunit
ndufs7_activity
Participant: Family: NADH-quinone oxidoreductase B/NDUFS7 (PSST) family
Family:
NADH-quinone oxidoreductase B/NDUFS7 (PSST) familyPANTHER:PTHR11995
Representative Members: NDUFS7 (human)UniProtKB:O75251

Function

NADH dehydrogenase (ubiquinone) activityGO:0008137
Substrates: electrons from the Fe-S wire ubiquinone
Products: ubiquinol (via the N2 cluster)

Locations

mitochondrial inner membraneGO:0005743

Carries the terminal N2 [4Fe-4S] cluster (electron donor to ubiquinone).

NDUFS8 (TYKY): N6a/N6b [4Fe-4S] subunit
ndufs8_activity
Participant: Family: NADH-quinone oxidoreductase I/NDUFS8 (TYKY) family
Family:
NADH-quinone oxidoreductase I/NDUFS8 (TYKY) familyPANTHER:PTHR10849
Representative Members: NDUFS8 (human)UniProtKB:O00217

Function

4 iron, 4 sulfur cluster bindingGO:0051539
Substrates: electrons along the Fe-S wire
Products: electrons relayed via N6a/N6b [4Fe-4S] clusters toward N2

Locations

mitochondrial inner membraneGO:0005743

Carries the N6a/N6b [4Fe-4S] clusters of the wire.

NDUFA9: SDR-fold junction accessory (39 kDa)
ndufa9_activity
Participant: Family: NDUFA9 / SDR-fold accessory family
Family:
NDUFA9 / SDR-fold accessory familyPANTHER:PTHR12126
Representative Members: NDUFA9 (human)UniProtKB:Q16795

Function

structural molecule activityGO:0005198
Substrates: (Q-module/membrane-arm junction; structural NADPH)
Products: stabilised Q-module/junction

Locations

mitochondrial inner membraneGO:0005743

Accessory subunit stabilising the Q-module/membrane-arm junction.

Part 3: peripheral-arm assembly/stability accessory
NDUFS4 accessory subunit (peripheral-arm assembly)Reactioncomplex_i_ndufs4

Annotons

NDUFS4: accessory/assembly subunit (18 kDa)
ndufs4_activity
Participant: Family: NDUFS4 accessory-subunit family
Family:
NDUFS4 accessory-subunit familyPANTHER:PTHR12219
Representative Members: NDUFS4 (human)UniProtKB:O43181

Processes

mitochondrial respiratory chain complex I assemblyGO:0032981

Locations

mitochondrial inner membraneGO:0005743

Accessory subunit required for peripheral-arm assembly and stability.

file:human/NDUFS4/NDUFS4-ai-review.yaml
accessory subunit required for assembly/stability of the peripheral arm; deficiency = Leigh syndrome (MC1DN1)