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 Rigoni
Investigation
;
Marta Carro-Alvarellos
Investigation
;
Masafumi Noguchi
Investigation
;
Martina Semenzato
Investigation
;
Federico Caicci
Methodology
;
Natascia Meneghetti
Investigation
;
Mattia Sturlese
Investigation
;
Stefano Moro
Investigation
;
Chiara Rampazzo
Investigation
;
Fabrizio Bezzo
Investigation
;
Leonardo Salviati
Resources
;
Gabriele Sales
Software
;
Chiara Romualdi
Software
;
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 functionalization
2025
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3544925
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