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Updated: Aug 5, 2026

An Improved Method to Isolate Mitochondrial Contact Sites
Published on: June 16, 2023
Integrative structure determination of a human mitochondrial contact site and cristae organizing system (MICOS)
Muskaan Jindal1, Rakesh Mahato2, Sreemoyee Das2
1National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, 560065, India.
Abstract:
The Mitochondrial contact site and Cristae Organizing System (MICOS) complex is an inner mitochondrial membrane (IMM) assembly present at the cristae junction. It is responsible for regulating cristae formation and remodeling. However, its structure is not known. We applied Bayesian integrative structure determination to characterize the structure of the Mic60, Mic19, Mic10, and Mic13-containing MICOS complex combining AlphaFold predictions with data from crosslinking mass spectrometry, biochemical assays, electron tomography, homology modeling, and sequence alignments. The integrative structure revealed novel mutual interfaces among Mic10N,C, Mic60LBS1,LBS2,mitofilin, and Mic13central,C, which were experimentally validated. Several likely-pathogenic missense mutations also localize to these novel interfaces, highlighting their importance. Our results indicate that Mic13 likely facilitates MICOS assembly by binding Mic10 in the IMM-proximal region and Mic60 in the intermembrane space. Taken together, our integrative approach sheds light on the structure and assembly of the MICOS complex.
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