Integrative structure determination of a human mitochondrial contact site and cristae organizing system (MICOS) sub-assembly
- 1NCBS, TIFR
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 sub-assembly 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. Several likely-pathogenic missense mutations also localize to these novel interfaces, highlighting their importance. Further, we investigated some of these interactions using binding assays on purified proteins and demonstrated direct interactions among Mic10-Mic13-Mic60. Our results support a bridging role for Mic13 in the 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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BibTeX
@misc{jindal2026integrative,
title = {{Integrative structure determination of a human mitochondrial contact site and cristae organizing system (MICOS) sub-assembly}},
author = {M. Jindal and R. Mahato and S. Das and A. Guha and K. Majila and S. Arvindekar and A. T. Vaidya and S. Viswanath},
howpublished = {bioRxiv},
year = {2026},
month = jul,
doi = {10.64898/2026.07.19.739404},
url = {https://www.biorxiv.org/content/10.64898/2026.07.19.739404v2},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Integrative structure determination of a human mitochondrial contact site and cristae organizing system (MICOS) sub-assembly
AU - M. Jindal
AU - R. Mahato
AU - S. Das
AU - A. Guha
AU - K. Majila
AU - S. Arvindekar
AU - A. T. Vaidya
AU - S. Viswanath
PY - 2026
DA - 2026/07/19
PB - bioRxiv
DO - 10.64898/2026.07.19.739404
UR - https://www.biorxiv.org/content/10.64898/2026.07.19.739404v2
AB - 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 sub-assembly 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. Several likely-pathogenic missense mutations also localize to these novel interfaces, highlighting their importance. Further, we investigated some of these interactions using binding assays on purified proteins and demonstrated direct interactions among Mic10-Mic13-Mic60. Our results support a bridging role for Mic13 in the 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.
ER -