Search
Browse
Statistics
Feeds

Integrative structural modelling reveals the human Mic60-Mic19 subcomplex as a diffusion barrier in mitochondria

[thumbnail of Original Article]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
8MB
[thumbnail of Supplementary Information] Other (Supplementary Information)
76MB

Item Type:Article
Title:Integrative structural modelling reveals the human Mic60-Mic19 subcomplex as a diffusion barrier in mitochondria
Creators: Nathanail, Evangelia ORCID logoORCID: https://orcid.org/0009-0004-9579-8074, Rolando, Edoardo ORCID logoORCID: https://orcid.org/0009-0001-8276-1406, Ruwolt, Max ORCID logoORCID: https://orcid.org/0009-0000-7220-406X, Zaporozhets, Iryna ORCID logoORCID: https://orcid.org/0000-0002-5846-3601, Liu, Fan ORCID logoORCID: https://orcid.org/0000-0002-2358-549X, Clementi, Cecilia ORCID logoORCID: https://orcid.org/0000-0001-9221-2358 and Daumke, Oliver ORCID logoORCID: 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:

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library