Integrative structure determination of a human mitochondrial contact site and cristae organizing system (MICOS) sub-assembly

Bayesian integrative modeling of the human MICOS Mic10, Mic13, Mic60, Mic19, and Mic10-containing sub-assembly reveals novel interfaces, including a Mic13 bridging role.

• Why it matters: MICOS regulates cristae formation and remodeling at cristae junctions, but the structure of its sub-assembly has been unclear, limiting interpretation of disease-linked variants.
• What they did: The team combined AlphaFold predictions with crosslinking mass spectrometry, biochemical assays, electron tomography, homology modeling, and sequence alignments to build an integrative structure.
• The result: Likely-pathogenic missense mutations map to the newly identified interfaces, and purified-protein binding assays show direct Mic10–Mic13–Mic60 interactions, supporting Mic13 bridging between IMM-proximal and intermembrane-space regions.

AI summary of the abstract · may contain errors · not medical advice · read the paper.