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| Item Type: | Article |
|---|---|
| Title: | Integrative structural modelling reveals the human Mic60-Mic19 subcomplex as a diffusion barrier in mitochondria |
| Creators: |
Nathanail, Evangelia  ORCID: https://orcid.org/0009-0004-9579-8074, Rolando, Edoardo ORCID: https://orcid.org/0009-0001-8276-1406, Ruwolt, Max ORCID: https://orcid.org/0009-0000-7220-406X, Zaporozhets, Iryna ORCID: https://orcid.org/0000-0002-5846-3601, Liu, Fan ORCID: https://orcid.org/0000-0002-2358-549X, Clementi, Cecilia ORCID: https://orcid.org/0000-0001-9221-2358 and Daumke, Oliver ORCID: https://orcid.org/0000-0002-6190-1414
|
| Abstract: | Mitochondrial crista junctions (CJs) operate as regulated gateways into the cristae microenvironment, whose protein, metabolite, and ion compositions are finely tuned for mitochondrial function. The Mic60-Mic19 complex of the mitochondrial contact site and cristae organizing system (MICOS) complex was suggested to span across CJs and act as a diffusion barrier, but little is known of how its dynamic architecture facilitates this task. To address this question, we determine the crystal structure of an amino-terminal dimeric helical bundle of human Mic60. These and previous structural and biochemical data are harnessed in molecular dynamic (MD) simulations to develop a dynamic model of the human tetrameric Mic60-Mic19 subcomplex in the CJ environment, to validate its architecture using in organello and in vitro cross-linking data and to computationally characterize its function as a diffusion barrier. Our integrative structural biology approach enables the functional investigation of flexible, multidomain protein complexes which escape conventional structural methods. |
| Keywords: | Diffusion, Mitochondria, Mitochondrial Membranes, Mitochondrial Proteins, Molecular Dynamics Simulation, Molecular Models, X-Ray Crystallography |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 17 |
| Number: | 1 |
| Page Range: | 10234 |
| Date: | 26 September 2026 |
| Official Publication: | https://doi.org/10.1038/s41467-026-77869-3 |
| PubMed: | View item in PubMed |
| Related to: |
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