Oxidative phosphorylation

Reviewing GO annotations across the five respiratory complexes, their carriers and assembly factors

AI Gene Review · projects/OXPHOS · 2026

Bottom line

  • OXPHOS makes most cellular ATP: four electron-transport complexes, two carriers, one ATP synthase, about 90 subunits plus assembly factors.
  • 36 of 38 prioritized human genes are reviewed: 1,330 annotations, 861 accepted, 152 over-annotated, 52 removed, 18 NEW.
  • One pattern throughout: subunits contributes_to the complex activity; assembly factors are not the enzyme.

What was reviewed, complex by complex

Why this pathway

  • Every complex is a multi-subunit machine, so the central question is who carries the activity: the complex, a catalytic subunit, or neither.
  • Assembly factors (SURF1, SCO1/2, COX10, COX15, BCS1L, TMEM70) often inherit the activity of the complex they build.
  • Dual roles need both kept apart: SDHA in TCA and ETC; CYCS in the ETC and apoptosis; ATP5F1B at the cell surface.
  • Disease genes (Leigh, paraganglioma, GRACILE, CoQ10 deficiency) make wrong annotations costly.

The subunit pattern

Role GO pattern Examples
Catalytic subunit enables own activity + contributes_to complex activity NDUFV1 electron transfer (NEW) + contributes to CI activity; SDHA; UQCRFS1
Non-catalytic subunit contributes_to only; direct oxidase row over-annotated COX6B1, COX4I2, COX6A1
Assembly factor assembly process or its own chemistry SURF1 → CIV assembly; COX10 heme O synthase; SCO1 copper chaperone
Inhibitor own MF ATP5IF1 → ATPase inhibitor activity

What a review looks like

SURF1: complex IV assembly is accepted as its core process. Its cytochrome-c oxidase activity and proton transport rows were removed.

Results by complex

Complex Genes Ann. ACCEPT Non-core Over-ann. MODIFY REMOVE NEW
I 5 252 187 38 15 4 4 2
II 5 196 135 29 12 9 6 5
III 4 112 66 9 27 3 5 2
IV 12 334 202 47 44 12 24 5
V 7 322 202 55 39 6 13 1
Carriers / CoQ / ETF 3 114 69 23 15 4 0 3

Counts from the 36 review YAMLs; 8 UNDECIDED (ATP5F1B 3, ATP5IF1 3, ACAD9 2) not shown. Complex IV includes its assembly factors and LRPPRC.

The OXPHOS module

modules/oxphos.yaml: each complex is one PROTEIN_COMPLEX node with a single complex-level activity; subunits are active units; NDH-2, AOX and bd-oxidase are variants.

Status and next steps

  • ✅ 36/38 prioritized genes reviewed; taxon-neutral OXPHOS module built.
  • ✅ Per-complex modules exist too (mitochondrial_complex_i_core … mitochondrial_complex_iv, ETF, CoQ10).
  • ⬜ COX7A2L (supercomplex factor, contested) and HCCS (cytochrome c heme lyase) not yet reviewed.
  • ✅ STATUS checklist updated for the 11 reviews done under other projects.

Read more: projects/OXPHOS.md · modules/oxphos.yaml · genes/human/<GENE>/