9WV1

Human TIM22 complex wtih substrate GGC1-sfGFP

Summary for 9WV1

• Entry DOI: 10.2210/pdb9wv1/pdb
• EMDB information: 66279
• Descriptor: Mitochondrial import inner membrane translocase subunit Tim22, Acylglycerol kinase, mitochondrial, Mitochondrial import inner membrane translocase subunit Tim29, ... (8 entities in total)
• Functional Keywords: mitochondria, protein translocation, translocase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 15
• Total formula weight: 227197.41

Authors

Liu, X.L.,Cai, H.J.,Li, L. (deposition date: 2025-09-19, release date: 2026-08-05)

Primary citation

Liu, X.,Cai, H.,Wang, H.,Zhou, X.,Zhang, Y.,Liu, S.,Zhu, J.,Li, L.
Direct coupling of human TOM and TIM22 complexes drives mitochondrial carrier import.
Nat.Struct.Mol.Biol., 2026

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 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.

PubMed: 42493623
DOI: 10.1038/s41594-026-01849-w

Experimental method

ELECTRON MICROSCOPY (3.1 Å)