Finding partners

The mitochondrial cristae — the folds of the inner mitochondrial membrane — undergo structural remodeling during respiration and apoptosis that also triggers outer mitochondrial membrane permeabilization. Such remodeling is likely to influence the composition and potentially the functional roles of the large protein complexes abundant in the cristae. Yet, how cristae remodeling affects the structure and function of these complexes remains undefined. To address this gap, Rigoni, Calvo, Glytsou et al. performed a comparative complexome analysis using native gel electrophoresis and liquid chromatography–mass spectrometry of respiring mitochondria from mouse hearts under control, permeabilized and remodeled conditions. Using these data, the team created two accessible online platforms called MARIGOLD and MitoCIAO.

MARIGOLD, the mitochondrial apoptotic remodeling complexome database, catalogs 627 mitochondrial proteins, enabling users to explore digital western blot profiles from native gels that report the localization of each protein in their respective native complexes. MitoCIAO (mitochondrial complexes interactome tool) leverages MARIGOLD to predict protein–protein interactions based on Spearman correlation coefficients across protein migration patterns, predicting co-migration and potential interactions within complexes. The team validated these tools by reproducing known interactions involving mitochondrial cristae organization system components and OPA1, the GTPase protein optic atrophy 1. Next, by profiling the dynamics of two complexes of ATAD3A, an ATPase membrane protein, with MARIGOLD, and identifying putative ATAD3A interactors with MitoCIAO, the team functionalized both complexes: the larger ATAD3A complex contains mitoribosome subunits and supports mitoribosome stability, while the smaller one contains OPA1 and is essential for cristae biogenesis. Overall, these two open-access platforms provide valuable tools for investigating the distribution and composition of mitochondrial complexes, enabling further opportunities for mitochondrial research.