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

Authors

Evangelia Nathanail, Edoardo Rolando, Max Ruwolt, Iryna Zaporozhets, Fan Liu, Cecilia Clementi, Oliver Daumke

Published in

Nature communications. Volume 17. Issue 1. Sep 26, 2026. Epub Sep 26, 2026.

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.

PMID:
42800801
Bibliographic data and abstract were imported from PubMed on 27 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.