Mitochondrial import pathways

One GO process term per import route, and a review of the human import machinery

AI Gene Review · projects/MITOCHONDRIAL_IMPORT_PATHWAYS · 2026

Bottom line

  • Mitochondrial proteins reach their compartment by six import routes, but GO grouped them inconsistently; GO issue #31711 proposed one term per route.
  • GO has added the route terms (GO:7770058, GO:7770059, GO:7770060, GO:7770061, GO:7770063) and reworded GO:0030150 and GO:0160203.
  • We reviewed 670 annotations on 23 human genes of the machinery; among them only MTCH2 yet carries a new route term (MTCH1 and yeast MIM1 also do, outside the set).

Six routes, six terms

Why this project

  • GO-CAM models of import need one process per route, so that TOM → SAM and TOM → TIM23 → PAM are not the same step.
  • Old terms mixed destination and machinery, and grouping terms (e.g. GO:0070585 protein localization to mitochondrion) collected annotations that belong to a specific route.
  • Reviewing the machinery shows which annotations would move to the new terms.

Actions per gene

Findings

  1. protein binding IPI rows removed on TOMM70 (11), CHCHD4 (5), TOMM40 (3), MTCH2 (3).
  2. Localization refined: SAMM50 mitochondrion → mitochondrial outer membrane; PMPCA → mitochondrial matrix.
  3. Wrong route: SAMM50 protein import into mitochondrial matrix → protein insertion into mitochondrial outer membrane.
  4. CHCHD4 protein-disulfide reductase → disulfide oxidoreductase activity: MIA40 oxidises its substrates.
  5. MTCH2 gains NEW GO:7770059 α-helical OM insertion, matching MTCH1 and yeast MIM1.

What a review looks like

MTCH2 review: the IBA mitochondrion row is marked over-annotated because the direct outer-membrane annotation says more; the propagation review records why.

Status and next steps

  • ✅ Issue #31711 read; 23 priority genes fetched and reviewed (the page checklist predated most of them).
  • ✅ GO added the route terms and reworded the matrix and IMS terms.
  • ⬜ Move reviews onto the new terms: TIMM22 → GO:7770061, SAMM50/MTX → GO:7770063, TIMM21 → GO:7770060.
  • ⬜ Two grouping terms proposed for obsoletion, GO:0070585 and GO:0072656, are still live in GO.

Read more: projects/MITOCHONDRIAL_IMPORT_PATHWAYS.md · genes/human/<GENE>/