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| Title | Direct coupling of human TOM and TIM22 complexes drives mitochondrial carrier import. |
|---|---|
| Journal, issue, pages | Nat Struct Mol Biol, Year 2026 |
| Publish date | Jul 23, 2026 |
Authors | Xiaolong Liu / Hongjun Cai / Hao Wang / Xueyin Zhou / Yutong Zhang / Shuai Liu / Jiajun Zhu / Long Li / ![]() |
| PubMed Abstract | Metabolite carriers that control essential metabolite transport are imported into mitochondria through the TOM and TIM22 complexes. How TOM and TIM22 coordinate in human mitochondria has remained ...Metabolite carriers that control essential metabolite transport are imported into mitochondria through the TOM and TIM22 complexes. How TOM and TIM22 coordinate in human mitochondria has remained largely unknown. Here we show that human TOM and TIM22 assemble into a supercomplex that seamlessly couples carrier translocation across the outer and inner membranes, unlike in yeast where the two complexes appear to function separately. Cryo-electron microscopy structures of the human TOM-TIM22 supercomplex reveal unpaired carrier transmembrane segments traversing the TOM channel along a hydrophobic path and exiting through an unexpected lateral groove outside the channel. The membrane-bound small Tim subunits provide the substrate entry site for TIM22, while a membrane-exposed groove of TIM22 serves as the exit for carrier insertion into the inner membrane. These findings provide insights into the human carrier translocation pathway at molecular resolution and establish the TOM-TIM22 supercomplex as a central organizing unit of mitochondrial carrier import. |
External links | Nat Struct Mol Biol / PubMed:42493623 |
| Methods | EM (single particle) |
| Resolution | 2.98 - 12.37 Å |
| Structure data | ![]() EMDB-66278: Human TOM-TIM22 supercomplex with substrate GGC1-sfGFP EMDB-66279, PDB-9wv1: EMDB-66280, PDB-9wv2: EMDB-66281, PDB-9wv3: |
| Chemicals | ![]() ChemComp-R16: ![]() ChemComp-3PE: ![]() ChemComp-PC1: |
| Source |
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Keywords | TRANSLOCASE / Mitochondria / Protein translocation |
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homo sapiens (human)
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