Mitochondrial proteins assemble dynamically in high molecular weight complexes essential for their functions. We generated and validated two searchable compendia of these mitochondrial complexes. Following identification by mass spectrometry of proteins in complexes separated using blue-native gel electrophoresis from unperturbed, cristae-remodeled, and outer membrane-permeabilized mitochondria, we created MARIGOLD, a Mitochondrial_Apoptotic_RemodelInG_cOmpLexome Database of 626 proteins. MARIGOLD elucidates how dynamically proteins distribute in complexes upon mitochondrial membrane remodeling. From MARIGOLD, we developed MitoCIAO, a Mitochondrial_Complexes_InterActome_tOol that by statistical correlation calculates likelihood of protein co-occurrence in complexes. MitoCIAO correctly predicted biologically validated interactions among components of the mitochondrial cristae organization system (MICOS) and Optic atrophy 1 (OPA1) complexes. We used MitoCIAO to functionalize two ATPase family AAA domain containing 3A (ATAD3A) complexes: one with OPA1 that regulates mitochondrial ultrastructure, the second containing ribosomal proteins that is essential for mitoribosome stability. These compendia reveal the dynamic nature of mitochondrial complexes and enable their functionalization
Marigold and MitoCIAO, two searchable compendia to visualize and functionalize protein complexes during mitochondrial remodeling
Giovanni RigoniInvestigation
;Marta Carro-AlvarellosInvestigation
;Masafumi NoguchiInvestigation
;Martina SemenzatoInvestigation
;Federico CaicciMethodology
;Natascia MeneghettiInvestigation
;Mattia SturleseInvestigation
;Stefano MoroInvestigation
;Chiara RampazzoInvestigation
;Fabrizio BezzoInvestigation
;Leonardo SalviatiResources
;Gabriele SalesSoftware
;Chiara RomualdiSoftware
;Luca Scorrano
Conceptualization
;Maria Eugenia Soriano
Conceptualization
2025
Abstract
Mitochondrial proteins assemble dynamically in high molecular weight complexes essential for their functions. We generated and validated two searchable compendia of these mitochondrial complexes. Following identification by mass spectrometry of proteins in complexes separated using blue-native gel electrophoresis from unperturbed, cristae-remodeled, and outer membrane-permeabilized mitochondria, we created MARIGOLD, a Mitochondrial_Apoptotic_RemodelInG_cOmpLexome Database of 626 proteins. MARIGOLD elucidates how dynamically proteins distribute in complexes upon mitochondrial membrane remodeling. From MARIGOLD, we developed MitoCIAO, a Mitochondrial_Complexes_InterActome_tOol that by statistical correlation calculates likelihood of protein co-occurrence in complexes. MitoCIAO correctly predicted biologically validated interactions among components of the mitochondrial cristae organization system (MICOS) and Optic atrophy 1 (OPA1) complexes. We used MitoCIAO to functionalize two ATPase family AAA domain containing 3A (ATAD3A) complexes: one with OPA1 that regulates mitochondrial ultrastructure, the second containing ribosomal proteins that is essential for mitoribosome stability. These compendia reveal the dynamic nature of mitochondrial complexes and enable their functionalizationPubblicazioni consigliate
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