Mitochondrial Complex I (NADH:ubiquinone oxidoreductase) accessory/supernumerary subunits; NDUFA1/2/5/6/8/10/11/12/13, NDUFB3/7/8/9/10/11, NDUFC2

Beyond its 14 conserved "core" subunits, mitochondrial respiratory Complex I (NADH:ubiquinone oxidoreductase) carries ~30 nuclear-encoded accessory (supernumerary) subunits that form a shell around the core L-shaped enzyme. These subunits are stable constituents of the mature holoenzyme (unlike the transient assembly factors) but are non-catalytic — they carry no redox cofactor and do not themselves perform the NADH:ubiquinone reaction. Their roles are structural: they stabilise and shield the core, seal the membrane arm, and are required for assembly and stability of a fully active complex. This module groups the human accessory subunits by which arm they decorate. The peripheral (matrix) arm accessory subunits — NDUFA2 (thioredoxin-fold), NDUFA5, NDUFA6, NDUFA12 (near the N/Q junction) and NDUFA13/GRIM-19 — buttress the flavoprotein and Q modules; NDUFA13 additionally has a well-documented moonlighting role as a negative regulator of STAT3 signalling and in apoptosis, curated separately from its structural role. The membrane arm accessory subunits — NDUFA1 (MWFE), NDUFA8 (twin-CX9C), NDUFA10, NDUFA11 (Tim17-like fold), NDUFB3, NDUFB7, NDUFB8, NDUFB9, NDUFB10 and NDUFB11 (several imported and disulfide-folded by the MIA40/CHCHD4 relay), and NDUFC2 — clamp the hydrophobic ND subunits. Loss of individual accessory subunits destabilises the holoenzyme and causes isolated mitochondrial complex I deficiency (Leigh syndrome, cardiomyopathy, leukoencephalopathy; NDUFB11 is X-linked, causing histiocytoid cardiomyopathy / MLS-like disease).

MODULE:complex_i_accessory_subunitsDRAFTProtein Complexmodules/complex_i_accessory_subunits.yaml
mitochondrial electron transport, NADH to ubiquinoneGO:0006120
GO:0006120
mitochondrial electron transport, NADH to ubiquinone
The accessory subunits structurally support the Complex I reaction, mitochondrial electron transport, NADH to ubiquinone (GO:0006120).
GO:0045271
respiratory chain complex I
All members are stable structural constituents of respiratory chain complex I (GO:0045271).
file:human/NDUFA1/NDUFA1-ai-review.yaml
NDUFA1 gene review (human)
The MWFE membrane-arm accessory subunit (UniProtKB:O15239, GO:0005198) matches the completed human NDUFA1 review.
file:human/NDUFA2/NDUFA2-ai-review.yaml
NDUFA2 gene review (human)
The B8 thioredoxin-fold peripheral accessory subunit (UniProtKB:O43678, GO:0005198) matches the completed human NDUFA2 review.
file:human/NDUFA5/NDUFA5-ai-review.yaml
NDUFA5 gene review (human)
The B13 peripheral-arm accessory subunit (UniProtKB:Q16718, GO:0005198) matches the completed human NDUFA5 review.
file:human/NDUFA6/NDUFA6-ai-review.yaml
NDUFA6 gene review (human)
The B14 peripheral-arm accessory subunit (UniProtKB:P56556, GO:0005198) matches the completed human NDUFA6 review.
file:human/NDUFA8/NDUFA8-ai-review.yaml
NDUFA8 gene review (human)
The PGIV twin-CX9C accessory subunit (UniProtKB:P51970, GO:0005198) matches the completed human NDUFA8 review.
file:human/NDUFA10/NDUFA10-ai-review.yaml
NDUFA10 gene review (human)
The dNK-fold (catalytically inactive) membrane-arm accessory subunit (UniProtKB:O95299, GO:0005198) matches the completed human NDUFA10 review.
file:human/NDUFA11/NDUFA11-ai-review.yaml
NDUFA11 gene review (human)
The B14.7 Tim17-fold membrane-arm accessory subunit (UniProtKB:Q86Y39, GO:0005198) matches the completed human NDUFA11 review.
file:human/NDUFA12/NDUFA12-ai-review.yaml
NDUFA12 gene review (human)
The B17.2 N/Q-junction accessory subunit (UniProtKB:Q9UI09, GO:0005198) matches the completed human NDUFA12 review.
file:human/NDUFA13/NDUFA13-ai-review.yaml
NDUFA13 gene review (human)
The GRIM-19 peripheral-arm accessory subunit (UniProtKB:Q9P0J0, GO:0005198) matches the completed human NDUFA13 review.
file:human/NDUFB3/NDUFB3-ai-review.yaml
NDUFB3 gene review (human)
The B12 membrane-arm accessory subunit (UniProtKB:O43676, GO:0005198) matches the completed human NDUFB3 review.
file:human/NDUFB7/NDUFB7-ai-review.yaml
NDUFB7 gene review (human)
The B18 twin-CX9C membrane-arm accessory subunit (UniProtKB:P17568, GO:0005198) matches the completed human NDUFB7 review.
file:human/NDUFB8/NDUFB8-ai-review.yaml
NDUFB8 gene review (human)
The ASHI membrane-arm accessory subunit (UniProtKB:O95169, GO:0005198) matches the completed human NDUFB8 review.
file:human/NDUFB9/NDUFB9-ai-review.yaml
NDUFB9 gene review (human)
The B22/LYRM3 membrane-arm accessory subunit (UniProtKB:Q9Y6M9, GO:0005198) matches the completed human NDUFB9 review.
file:human/NDUFB10/NDUFB10-ai-review.yaml
NDUFB10 gene review (human)
The PDSW twin-CX9C membrane-arm accessory subunit (UniProtKB:O96000, GO:0005198) matches the completed human NDUFB10 review.
file:human/NDUFB11/NDUFB11-ai-review.yaml
NDUFB11 gene review (human)
The ESSS X-linked membrane-arm accessory subunit (UniProtKB:Q9NX14, GO:0005198) matches the completed human NDUFB11 review.
file:human/NDUFC2/NDUFC2-ai-review.yaml
NDUFC2 gene review (human)
The B14.5b membrane-arm accessory subunit (UniProtKB:O95298, GO:0005198) matches the completed human NDUFC2 review.
3Nodes
2Parts
0Variant Sets
0Variants
16Annotons
1Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:complex_i_accessory_subunits 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 (16/16 grounded genes reviewed)

16 complete review(s) · 0 with deep research · 0 missing review · 16 reviewed but lacking deep research

Gene Review Complete Deep research
NDUFA1 O15239 ✓ ✓ ✗
NDUFA10 O95299 ✓ ✓ ✗
NDUFA11 Q86Y39 ✓ ✓ ✗
NDUFA12 Q9UI09 ✓ ✓ ✗
NDUFA13 Q9P0J0 ✓ ✓ ✗
NDUFA2 O43678 ✓ ✓ ✗
NDUFA5 Q16718 ✓ ✓ ✗
NDUFA6 P56556 ✓ ✓ ✗
NDUFA8 P51970 ✓ ✓ ✗
NDUFB10 O96000 ✓ ✓ ✗
NDUFB11 Q9NX14 ✓ ✓ ✗
NDUFB3 O43676 ✓ ✓ ✗
NDUFB7 P17568 ✓ ✓ ✗
NDUFB8 O95169 ✓ ✓ ✗
NDUFB9 Q9Y6M9 ✓ ✓ ✗
NDUFC2 O95298 ✓ ✓ ✗

Details

Context
mitochondrial inner membraneGO:0005743
Complex I (NADH:ubiquinone oxidoreductase) accessory/supernumerary subunitsProtein Complexcomplex_i_accessory_subunits
mitochondrial electron transport, NADH to ubiquinoneGO:0006120
Context
mitochondrial inner membraneGO:0005743

Accessory/supernumerary (non-core) subunits of mitochondrial respiratory Complex I (NADH:ubiquinone oxidoreductase), grouped by arm and grounded to the completed human gene reviews. Peripheral (matrix) arm: NDUFA2 (O43678), NDUFA5 (Q16718), NDUFA6 (P56556), NDUFA12 (Q9UI09), NDUFA13 (Q9P0J0, GRIM-19). Membrane arm: NDUFA1 (O15239), NDUFA8 (P51970), NDUFA10 (O95299), NDUFA11 (Q86Y39), NDUFB3 (O43676), NDUFB7 (P17568), NDUFB8 (O95169), NDUFB9 (Q9Y6M9), NDUFB10 (O96000), NDUFB11 (Q9NX14), NDUFC2 (O95298). Every member is a non-catalytic structural constituent (GO:0005198 structural molecule activity) that contributes to, but does not itself enable, the complex-level NADH dehydrogenase (ubiquinone) activity (GO:0008137); all are part_of respiratory chain complex I (GO:0045271) at the mitochondrial inner membrane (GO:0005743). Notable subunits: NDUFA10 retains a deoxyribonucleoside-kinase fold but is catalytically inactive (pseudokinase — no kinase MF assigned); NDUFA13/GRIM-19 has a genuine STAT3-inhibition/apoptosis moonlighting role that is curated as a separate non-core function in its gene review; several (NDUFA8/NDUFB7/NDUFB10) are twin-CX9C proteins imported by the MIA40/CHCHD4 disulfide relay. This module complements the merged mitochondrial_complex_i_core (catalytic N+Q modules) and complex_i_assembly_factors modules; together they cover the nuclear-encoded Complex I proteome (the mtDNA-encoded ND1-6/ND4L membrane subunits are curated separately). GO term ids/labels were verified against the local go.db. Disorders: isolated mitochondrial complex I deficiency — Leigh syndrome, cardiomyopathy, leukoencephalopathy; NDUFB11 is X-linked (histiocytoid cardiomyopathy / MLS-like).

Connections

The peripheral-arm and membrane-arm accessory shells together stabilise the core L-shaped Complex I; they are co-assembled constituents of the same holoenzyme rather than a sequential pathway (the connection denotes structural interdependence within the mature complex).
Part 1: peripheral (matrix) arm accessory subunits
Peripheral-arm accessory subunits (NDUFA2/5/6/12/13)Protein Complexci_peripheral_accessory

Annotons

NDUFA2 (B8): thioredoxin-fold peripheral accessory
ndufa2_activity
Participant: Family: NDUFA2 / B8 thioredoxin-fold accessory family
Family:
NDUFA2 / B8 thioredoxin-fold accessory familyPANTHER:PTHR12878
Representative Members: NDUFA2 (human)UniProtKB:O43678

Function

structural molecule activityGO:0005198
Substrates: (peripheral-arm scaffold)
Products: stabilised Complex I peripheral arm

Locations

mitochondrial inner membraneGO:0005743

Thioredoxin-fold peripheral-arm accessory subunit (non-catalytic).

NDUFA5 (B13): peripheral-arm accessory
ndufa5_activity
Participant: Family: NDUFA5 / B13 accessory family
Family:
NDUFA5 / B13 accessory familyPANTHER:PTHR12653
Representative Members: NDUFA5 (human)UniProtKB:Q16718

Function

structural molecule activityGO:0005198
Substrates: (peripheral-arm scaffold)
Products: stabilised Complex I peripheral arm

Locations

mitochondrial inner membraneGO:0005743

Peripheral-arm accessory subunit (non-catalytic).

NDUFA6 (B14): peripheral-arm accessory
ndufa6_activity
Participant: Family: NDUFA6 / B14 (LYRM6) accessory family
Family:
NDUFA6 / B14 (LYRM6) accessory familyPANTHER:PTHR12964
Representative Members: NDUFA6 (human)UniProtKB:P56556

Function

structural molecule activityGO:0005198
Substrates: (Q-module region scaffold)
Products: stabilised Complex I Q-module region

Locations

mitochondrial inner membraneGO:0005743

Peripheral-arm accessory subunit near the Q site (non-catalytic).

NDUFA12 (B17.2): N/Q-junction accessory
ndufa12_activity
Participant: Family: NDUFA12 / B17.2 accessory family
Family:
NDUFA12 / B17.2 accessory familyPANTHER:PTHR12910
Representative Members: NDUFA12 (human)UniProtKB:Q9UI09

Function

structural molecule activityGO:0005198
Substrates: (N/Q-module junction scaffold)
Products: stabilised Complex I N/Q junction

Locations

mitochondrial inner membraneGO:0005743

N/Q-module junction accessory subunit (non-catalytic; not the NDUFAF2 assembly factor).

NDUFA13 (GRIM-19): peripheral-arm accessory
ndufa13_activity
Participant: Family: NDUFA13 / GRIM-19 accessory family
Family:
NDUFA13 / GRIM-19 accessory familyPANTHER:PTHR12966
Representative Members: NDUFA13 (human)UniProtKB:Q9P0J0

Function

structural molecule activityGO:0005198
Substrates: (peripheral-arm scaffold)
Products: stabilised Complex I peripheral arm

Locations

mitochondrial inner membraneGO:0005743

Peripheral-arm accessory subunit (GRIM-19; STAT3/apoptosis moonlighting is a separate non-core role).

Part 2: membrane arm accessory subunits
Membrane-arm accessory subunits (NDUFA1/8/10/11, NDUFB3/7/8/9/10/11, NDUFC2)Protein Complexci_membrane_accessory

Annotons

NDUFA1 (MWFE): membrane-arm accessory
ndufa1_activity
Participant: Family: NDUFA1 / MWFE accessory family
Family:
NDUFA1 / MWFE accessory familyPANTHER:PTHR17098
Representative Members: NDUFA1 (human)UniProtKB:O15239

Function

structural molecule activityGO:0005198
Substrates: (membrane-arm scaffold)
Products: stabilised Complex I membrane arm

Locations

mitochondrial inner membraneGO:0005743

MWFE membrane-arm accessory subunit (non-catalytic).

NDUFA8 (PGIV): twin-CX9C membrane-arm accessory
ndufa8_activity
Participant: Family: NDUFA8 / PGIV twin-CX9C accessory family
Family:
NDUFA8 / PGIV twin-CX9C accessory familyPANTHER:PTHR13344
Representative Members: NDUFA8 (human)UniProtKB:P51970

Function

structural molecule activityGO:0005198
Substrates: (membrane-arm scaffold)
Products: stabilised Complex I membrane arm

Locations

mitochondrial inner membraneGO:0005743

Twin-CX9C membrane-arm accessory subunit (non-catalytic).

NDUFA10: dNK-fold membrane-arm accessory
ndufa10_activity
Participant: Family: NDUFA10 / deoxyribonucleoside-kinase-fold accessory family
Family:
NDUFA10 / deoxyribonucleoside-kinase-fold accessory familyPANTHER:PTHR10513
Representative Members: NDUFA10 (human)UniProtKB:O95299

Function

structural molecule activityGO:0005198
Substrates: (membrane-arm scaffold)
Products: stabilised Complex I membrane arm

Locations

mitochondrial inner membraneGO:0005743

dNK-fold (catalytically inactive) membrane-arm accessory subunit.

NDUFA11 (B14.7): Tim17-fold membrane-arm accessory
ndufa11_activity
Participant: Family: NDUFA11 / B14.7 Tim17-fold accessory family
Family:
NDUFA11 / B14.7 Tim17-fold accessory familyPANTHER:PTHR21382
Representative Members: NDUFA11 (human)UniProtKB:Q86Y39

Function

structural molecule activityGO:0005198
Substrates: (membrane-arm scaffold)
Products: stabilised Complex I membrane arm

Locations

mitochondrial inner membraneGO:0005743

Tim17-fold membrane-arm accessory subunit (non-catalytic).

NDUFB3 (B12): membrane-arm accessory
ndufb3_activity
Participant: Family: NDUFB3 / B12 accessory family
Family:
NDUFB3 / B12 accessory familyPANTHER:PTHR15082
Representative Members: NDUFB3 (human)UniProtKB:O43676

Function

structural molecule activityGO:0005198
Substrates: (membrane-arm scaffold)
Products: stabilised Complex I membrane arm

Locations

mitochondrial inner membraneGO:0005743

Membrane-arm accessory subunit (non-catalytic).

NDUFB7 (B18): twin-CX9C membrane-arm accessory
ndufb7_activity
Participant: Family: NDUFB7 / B18 twin-CX9C accessory family
Family:
NDUFB7 / B18 twin-CX9C accessory familyPANTHER:PTHR20900
Representative Members: NDUFB7 (human)UniProtKB:P17568

Function

structural molecule activityGO:0005198
Substrates: (membrane-arm scaffold)
Products: stabilised Complex I membrane arm

Locations

mitochondrial inner membraneGO:0005743

Twin-CX9C membrane-arm accessory subunit (non-catalytic).

NDUFB8 (ASHI): membrane-arm accessory
ndufb8_activity
Participant: Family: NDUFB8 / ASHI accessory family
Family:
NDUFB8 / ASHI accessory familyPANTHER:PTHR12840
Representative Members: NDUFB8 (human)UniProtKB:O95169

Function

structural molecule activityGO:0005198
Substrates: (membrane-arm scaffold)
Products: stabilised Complex I membrane arm

Locations

mitochondrial inner membraneGO:0005743

Membrane-arm accessory subunit (non-catalytic).

NDUFB9 (B22/LYRM3): membrane-arm accessory
ndufb9_activity
Participant: Family: NDUFB9 / B22 (LYRM3) accessory family
Family:
NDUFB9 / B22 (LYRM3) accessory familyPANTHER:PTHR12868
Representative Members: NDUFB9 (human)UniProtKB:Q9Y6M9

Function

structural molecule activityGO:0005198
Substrates: (membrane-arm scaffold)
Products: stabilised Complex I membrane arm

Locations

mitochondrial inner membraneGO:0005743

LYR-family membrane-arm accessory subunit (non-catalytic).

NDUFB10 (PDSW): twin-CX9C membrane-arm accessory
ndufb10_activity
Participant: Family: NDUFB10 / PDSW twin-CX9C accessory family
Family:
NDUFB10 / PDSW twin-CX9C accessory familyPANTHER:PTHR13094
Representative Members: NDUFB10 (human)UniProtKB:O96000

Function

structural molecule activityGO:0005198
Substrates: (membrane-arm scaffold)
Products: stabilised Complex I membrane arm

Locations

mitochondrial inner membraneGO:0005743

Twin-CX9C membrane-arm accessory subunit (non-catalytic).

NDUFB11 (ESSS): X-linked membrane-arm accessory
ndufb11_activity
Participant: Family: NDUFB11 / ESSS accessory family
Family:
NDUFB11 / ESSS accessory familyPANTHER:PTHR13327
Representative Members: NDUFB11 (human)UniProtKB:Q9NX14

Function

structural molecule activityGO:0005198
Substrates: (membrane-arm scaffold)
Products: stabilised Complex I membrane arm

Locations

mitochondrial inner membraneGO:0005743

X-linked membrane-arm accessory subunit (non-catalytic).

NDUFC2 (B14.5b): membrane-arm accessory
ndufc2_activity
Participant: Family: NDUFC2 / B14.5b accessory family
Family:
NDUFC2 / B14.5b accessory familyPANTHER:PTHR13099
Representative Members: NDUFC2 (human)UniProtKB:O95298

Function

structural molecule activityGO:0005198
Substrates: (membrane-arm scaffold)
Products: stabilised Complex I membrane arm

Locations

mitochondrial inner membraneGO:0005743

Membrane-arm accessory subunit (non-catalytic).