It is found that the MIC10 proteins Mic10, Mic26, and Mic27 strongly recruit cardiolipin at conserved positive loop motifs, driving oligomerization of these subunits and resulting in the stabilization of curvature in model membranes.
Abstract
Mitochondrial cristae are essential for respiration, yet the molecular basis of how the high curvature of these membrane folds is maintained remains unclear. Using structure prediction tools and multiscale simulations, we examined the role of the MIC10 subcomplex of the mitochondrial contact site and cristae organizing system (MICOS). We found that the MIC10 proteins Mic10, Mic26, and Mic27 strongly recruit cardiolipin at conserved positive loop motifs, driving oligomerization of these subunits and resulting in the stabilization of curvature in model membranes. Reconstruction of the full MIC10 complex in a realistic crista junction setup shows its capability to maintain membrane bending, while intrinsically disordered regions may form a permeability barrier between cristae and the intermembrane space. These findings provide a mechanistic model for cristae curvature formation and suggest how MICOS components cooperate with cardiolipins to maintain mitochondrial architecture.
The few knowns about crista formation in a handful of organisms are highlighted to guide research into the many unknowns about how complex subcompartments represented by mitochondrial cristae are formed.
Lilia Colina-Tenorio, Martina Bohuslavová, Alexander W. Bruce et al.· Biochemical Society Transact...· 0 citations
The results indicate that Mic13 likely facilitates MICOS assembly by binding Mic10 in the IMM-proximal region and Mic60 in the intermembrane space, and several likely-pathogenic missense mutations also localize to these novel interfaces, highlighting their importance.
Muskaan Jindal, Rakesh Mahato, Sreemoyee Das et al.· bioRxiv· 0 citations
It is demonstrated that all MICOS subunits assemble onto precursor cristae, retaining conserved interactions with both outer and inner membrane protein machineries, establishing that MICOS assembly precedes cellular respiratory competence and expand its interaction landscape in trypanosomatids.
Michala Boudová, Teresa Wagner, Tomáš Bílý et al.· bioRxiv· 1 citation
A simple, quick, and reproducible protocol for reconstituting respiratory SCs into liposomes that allows for testing the effects of varying lipid compositions, protein concentration, and membrane potential on the function of respiratory SCs, providing a valuable tool for future mechanistic studies.
A. Padavannil, Pei-Yi Liu, J. Letts· Journal of Visualized Experi...· 0 citations
The solution structure of mature Saccharomyces cerevisiae Mba1 is determined using multidimensional nuclear magnetic resonance (NMR) spectroscopy and reveals a compact α + β fold with a central hydrophobic cavity and distinct charged surface regions, providing a structural framework for interpreting previous functional...
Jing Yang, Mao-Sen Ruan, Dong-Shuai Bai et al.· Journal of Structural Biolog...· 0 citations
This work describes a multi-stage transport pipeline—the TH–isocitrate dehydrogenase axis—wherein matrix-generated reducing equivalents are exported into the cytoplasm via an irreversible isocitrate/α-ketoglutarate loop and highlights the role of compartmentalization in ATP transport and utilization processes.
A. Panov, S. V. Nesterov, L. Yaguzhinsky· Current Issues in Molecular...· 0 citations
A new machine-learning framework aims to improve the success rate of computational protein design while moving away from results that reproduce sequences found in nature.
