MARIGOLD and MitoCIAO, two searchable compendia to visualize and functionalize protein complexes during mitochondrial remodeling.

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 e...

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Detalles Bibliográficos
Autores: Rigoni, Giovanni, Calvo, Enrique, Glytsou, Christina, Carro-Alvarellos, Marta, Noguchi, Masafumi, Semenzato, Martina, Quirin, Charlotte, Caicci, Federico, Meneghetti, Natascia, Sturlese, Mattia, Ishihara, Takaya, Moro, Stefano, Rampazzo, Chiara, Ishihara, Naotada, Bezzo, Fabrizio, Salviati, Leonardo, Vazquez, Jesùs, Sales, Gabriele, Romualdi, Chiara, Enriquez, Jose Antonio, Scorrano, Luca, Soriano, Maria Eugenia
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/26814
Acceso en línea:https://hdl.handle.net/20.500.12105/26814
Access Level:acceso abierto
Palabra clave:ATAD3A
OPA1
cristae remodeling
interactome
mitochondria
mitochondrial complexes
mitoribosome stability
Descripción
Sumario: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 627 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 the likelihood of protein cooccurrence 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 and the second containing ribosomal proteins that is essential for mitoribosome stability. These compendia reveal the dynamic nature of mitochondrial complexes and enable their functionalization.

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