Mitochondrial Complex IV (cytochrome c oxidase) assembly factors; TACO1/COA3/COX11/COA6/COX16/COA5/COX18/COA7/PET100/PET117

Assembly of cytochrome c oxidase (Complex IV) around its three mtDNA-encoded catalytic subunits (MT-CO1, MT-CO2, MT-CO3) is a highly ordered, factor-dependent process, because the copper and heme redox centres must be built into hydrophobic membrane proteins in the correct sequence. This module groups the dedicated assembly factors by the step they serve. Synthesis of the central MT-CO1 subunit is activated by the matrix RNA-binding translational activator TACO1 (which binds the MT-CO1 mRNA on the mitoribosome), and the nascent MT-CO1 is captured and stabilised by the MITRAC module (COA3/CCDC56 with COX14) that couples its translation to assembly. The MT-CO1 CuB site is metallated by the copper chaperone COX11, while the MT-CO2 CuA site is built by an intermembrane-space copper-relay/thiol-redox system — COA6 and COA7 (twin CX9C protein-disulfide reductases), COX16 and COA5 — acting with the SCO1/SCO2 metallochaperones (reviewed elsewhere). MT-CO2 itself is threaded into the membrane by the OXA1L-family insertase COX18 (with COX20). Finally, PET100 and PET117 are small chaperones that promote incorporation of the early nuclear-encoded subunits (COX7/COX8) to complete the holoenzyme. Loss of any factor causes mitochondrial complex IV (cytochrome c oxidase) deficiency — Leigh syndrome, fatal infantile cardioencephalomyopathy (COA5/COA6), axonal neuropathy with leukoencephalopathy (COA7) and other encephalopathies.

MODULE:complex_iv_assembly_factorsDRAFTMetabolic Pathwaymodules/complex_iv_assembly_factors.yaml
mitochondrial respiratory chain complex IV assemblyGO:0033617
GO:0033617
mitochondrial respiratory chain complex IV assembly
The module is grounded in mitochondrial respiratory chain complex IV assembly (GO:0033617); it groups the dedicated factors that build cytochrome c oxidase.
Reactome:R-HSA-9864848
Complex IV assembly
The MT-CO1/MT-CO2 metallation and subunit-incorporation steps follow the human Reactome "Complex IV assembly" pathway (R-HSA-9865449 CuB, R-HSA-9865630 CuA, R-HSA-9902096 COX18).
file:human/TACO1/TACO1-ai-review.yaml
TACO1 gene review (human)
The MT-CO1 translational-activator step (UniProtKB:Q9BSH4, GO:0097177) matches the completed human TACO1 review.
file:human/COA3/COA3-ai-review.yaml
COA3 gene review (human)
The MITRAC MT-CO1 stabilisation step (UniProtKB:Q9Y2R0) matches the completed human COA3 review.
file:human/COX11/COX11-ai-review.yaml
COX11 gene review (human)
The MT-CO1 CuB metallation step (UniProtKB:Q9Y6N1, GO:0016531) matches the completed human COX11 review.
file:human/COA6/COA6-ai-review.yaml
COA6 gene review (human)
The MT-CO2 CuA copper-relay step (UniProtKB:Q5JTJ3, GO:0015035) matches the completed human COA6 review.
file:human/COX16/COX16-ai-review.yaml
COX16 gene review (human)
The MT-CO2 CuA assembly step (UniProtKB:Q9P0S2) matches the completed human COX16 review.
file:human/COA5/COA5-ai-review.yaml
COA5 gene review (human)
The early MT-CO2 maturation step (UniProtKB:Q86WW8) matches the completed human COA5 review.
file:human/COX18/COX18-ai-review.yaml
COX18 gene review (human)
The MT-CO2 membrane-insertion step (UniProtKB:Q8N8Q8, GO:0032977) matches the completed human COX18 review.
file:human/COA7/COA7-ai-review.yaml
COA7 gene review (human)
The IMS thiol-redox assembly step (UniProtKB:Q96BR5, GO:0015035) matches the completed human COA7 review.
file:human/PET100/PET100-ai-review.yaml
PET100 gene review (human)
The early-subunit (COX7/COX8) incorporation step (UniProtKB:P0DJ07) matches the completed human PET100 review.
file:human/PET117/PET117-ai-review.yaml
PET117 gene review (human)
The PET100-related early-assembly step (UniProtKB:Q6UWS5) matches the completed human PET117 review.
6Nodes
5Parts
0Variant Sets
0Variants
10Annotons
4Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:complex_iv_assembly_factors 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) · 0 with deep research · 0 missing review · 10 reviewed but lacking deep research

Gene Review Complete Deep research
COA3 Q9Y2R0 ✓ ✓ ✗
COA5 Q86WW8 ✓ ✓ ✗
COA6 Q5JTJ3 ✓ ✓ ✗
COA7 Q96BR5 ✓ ✓ ✗
COX11 Q9Y6N1 ✓ ✓ ✗
COX16 Q9P0S2 ✓ ✓ ✗
COX18 Q8N8Q8 ✓ ✓ ✗
PET100 P0DJ07 ✓ ✓ ✗
PET117 Q6UWS5 ✓ ✓ ✗
TACO1 Q9BSH4 ✓ ✓ ✗

Details

Context
mitochondrial inner membraneGO:0005743 mitochondrial intermembrane spaceGO:0005758
Complex IV (cytochrome c oxidase) assembly factorsMetabolic Pathwaycomplex_iv_assembly_factors
mitochondrial respiratory chain complex IV assemblyGO:0033617
Context
mitochondrial inner membraneGO:0005743 mitochondrial intermembrane spaceGO:0005758

Complex IV (cytochrome c oxidase) assembly factors, grouped by the step they serve and grounded to the human proteins TACO1 (UniProtKB:Q9BSH4, GO:0097177), COA3 (Q9Y2R0), COX11 (Q9Y6N1, GO:0016531), COA6 (Q5JTJ3, GO:0015035), COA7 (Q96BR5, GO:0015035), COX16 (Q9P0S2), COA5 (Q86WW8), COX18 (Q8N8Q8, GO:0032977), PET100 (P0DJ07) and PET117 (Q6UWS5); all carry GO:0033617 (Complex IV assembly). 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. Each factor uses a PANTHER family selector; the catalytically-informative factors (TACO1 mitoribosome binding, COX11 copper chaperone, COX18 insertase, COA6/COA7 protein-disulfide reductase) carry an MF, while the purely scaffolding factors (COA3, COX16, COA5, PET100, PET117) are modelled by their GO:0033617 BP role. The mtDNA-encoded catalytic subunits (MT-CO1/CO2/CO3) and the copper/heme metallochaperones already reviewed on main (SCO1/SCO2 GO:0016531, COX10 heme O, COX15 heme a, SURF1, COX17) are the substrates/partners of these factors; the nuclear structural subunits and their holoenzyme are the sibling Complex IV module. The current Complex IV membership term is GO:0045277 (GO:0005751 obsolete); the assembly BP is GO:0033617. Disorders: mitochondrial complex IV deficiency — Leigh syndrome (TACO1, PET100), fatal infantile cardioencephalomyopathy (COA5, COA6), axonal neuropathy with leukoencephalopathy / SCAN3 (COA7), and other encephalopathies (COA3, COX16, COX18, PET117).

Connections

mtco1_synthesis -> cub_metallation Provides Input For
The stabilised MT-CO1 produced with TACO1/COA3 is metallated at CuB by COX11.
cub_metallation -> subunit_incorporation Provides Input For
The metallated MT-CO1 seed recruits the nuclear subunits via PET100/PET117.
mtco2_insertion -> cua_metallation Provides Input For
Membrane-inserted MT-CO2 (COX18) is CuA-metallated by the COA6/COA7/COX16/COA5 relay.
cua_metallation -> subunit_incorporation Provides Input For
Metallated MT-CO2 joins the MT-CO1 module as the nuclear subunits are incorporated.
Part 1: MT-CO1 synthesis and stabilisation
MT-CO1 translation activation and MITRAC stabilisationReactionmtco1_synthesis

Annotons

TACO1: MT-CO1 translational activator
taco1_activity
Participant: Family: TACO1 / S4-domain translational activator family
Family:
TACO1 / S4-domain translational activator familyPANTHER:PTHR12532
Representative Members: TACO1 (human)UniProtKB:Q9BSH4

Function

mitochondrial ribosome bindingGO:0097177
Substrates: MT-CO1 (COX1) mitochondrial mRNA / mitoribosome
Products: translated MT-CO1 protein

Locations

mitochondrial matrixGO:0005759

Activates translation of the MT-CO1 catalytic core subunit.

COA3 (MITRAC12/CCDC56): MT-CO1 stabilisation
coa3_activity
Participant: Family: COA3 / MITRAC12 family
Family:
COA3 / MITRAC12 familyPANTHER:PTHR15642
Representative Members: COA3 (human)UniProtKB:Q9Y2R0

Processes

mitochondrial respiratory chain complex IV assemblyGO:0033617

Locations

mitochondrial inner membraneGO:0005743

Stabilises nascent MT-CO1 in the MITRAC module.

file:human/COA3/COA3-ai-review.yaml
MITRAC component (with COX14) that captures/stabilises nascent MT-CO1 and couples its translation to assembly
Part 2: MT-CO1 CuB copper metallation
copper insertion into the MT-CO1 CuB siteReactioncub_metallation

Annotons

COX11: CuB copper chaperone
cox11_activity
Participant: Family: COX11 copper chaperone family
Family:
COX11 copper chaperone familyPANTHER:PTHR21320
Representative Members: COX11 (human)UniProtKB:Q9Y6N1

Function

copper chaperone activityGO:0016531
Substrates: copper (from COX17) MT-CO1 apo-CuB site
Products: metallated MT-CO1 CuB site

Locations

mitochondrial inner membraneGO:0005743

Metallates the MT-CO1 CuB centre.

Part 3: MT-CO2 membrane insertion
MT-CO2 C-terminal membrane insertionReactionmtco2_insertion

Annotons

COX18: MT-CO2 membrane insertase
cox18_activity
Participant: Family: OXA1L/YidC insertase family (COX18)
Family:
OXA1L/YidC insertase family (COX18)PANTHER:PTHR12428
Representative Members: COX18 (human)UniProtKB:Q8N8Q8

Function

membrane insertase activityGO:0032977
Substrates: newly-synthesised MT-CO2 (C-terminal tail)
Products: membrane-inserted MT-CO2

Locations

mitochondrial inner membraneGO:0005743

Inserts the MT-CO2 C-terminus into the inner membrane.

Part 4: MT-CO2 CuA copper-relay and thiol-redox metallation
MT-CO2 CuA site copper delivery and disulfide relayReactioncua_metallation

Annotons

COA6: CuA copper-relay disulfide reductase
coa6_activity
Participant: Family: COA6 twin-CX9C family
Family:
COA6 twin-CX9C familyPANTHER:PTHR46690
Representative Members: COA6 (human)UniProtKB:Q5JTJ3

Function

protein-disulfide reductase activityGO:0015035
Substrates: SCO1/SCO2/MT-CO2 copper-coordinating disulfides
Products: reduced (thiol) copper-ligand cysteines for CuA metallation

Locations

mitochondrial intermembrane spaceGO:0005758

Thiol-redox relay for MT-CO2 CuA metallation.

COA7: IMS Sel1-repeat disulfide reductase
coa7_activity
Participant: Family: COA7 / Sel1-repeat family
Family:
COA7 / Sel1-repeat familyPANTHER:PTHR13891
Representative Members: COA7 (human)UniProtKB:Q96BR5

Function

protein-disulfide reductase activityGO:0015035
Substrates: IMS assembly-intermediate disulfides
Products: reduced assembly intermediates

Locations

mitochondrial intermembrane spaceGO:0005758

IMS thiol-redox assembly factor.

COX16: MT-CO2 CuA assembly factor
cox16_activity
Participant: Family: COX16 assembly-factor family
Family:
COX16 assembly-factor familyPANTHER:PTHR17130
Representative Members: COX16 (human)UniProtKB:Q9P0S2

Processes

mitochondrial respiratory chain complex IV assemblyGO:0033617

Locations

mitochondrial inner membraneGO:0005743

MT-CO2 CuA maturation factor.

file:human/COX16/COX16-ai-review.yaml
assembly factor implicated in MT-CO2 maturation / CuA formation with SCO1/SCO2/COA6/COX20
COA5: early MT-CO2 maturation factor
coa5_activity
Participant: Family: COA5 / PET191 twin-CX9C family
Family:
COA5 / PET191 twin-CX9C familyPANTHER:PTHR28627
Representative Members: COA5 (human)UniProtKB:Q86WW8

Processes

mitochondrial respiratory chain complex IV assemblyGO:0033617

Locations

mitochondrial intermembrane spaceGO:0005758

Early MT-CO2 maturation factor.

file:human/COA5/COA5-ai-review.yaml
twin-CX9C IMS factor for early MT-CO2 maturation; deficiency = fatal infantile cardioencephalomyopathy
Part 5: incorporation of the early nuclear subunits
incorporation of the early COX7/COX8 nuclear subunitsReactionsubunit_incorporation

Annotons

PET100: early-subunit incorporation chaperone
pet100_activity
Participant: Family: PET100 family
Family:
PET100 familyPANTHER:PTHR33968
Representative Members: PET100 (human)UniProtKB:P0DJ07

Processes

mitochondrial respiratory chain complex IV assemblyGO:0033617

Locations

mitochondrial inner membraneGO:0005743

Promotes incorporation of the early nuclear subunits.

file:human/PET100/PET100-ai-review.yaml
COX-specific chaperone promoting incorporation of the early COX7/COX8 nuclear subunits; deficiency = Leigh syndrome
PET117: PET100-related early-assembly chaperone
pet117_activity
Participant: Family: PET117 family
Family:
PET117 familyPANTHER:PTHR28163
Representative Members: PET117 (human)UniProtKB:Q6UWS5

Processes

mitochondrial respiratory chain complex IV assemblyGO:0033617

Locations

mitochondrial inner membraneGO:0005743

PET100-related early-assembly chaperone.

file:human/PET117/PET117-ai-review.yaml
small Complex IV assembly chaperone functionally related to PET100; deficiency = MC4DN19 / neurodevelopmental disorder