MARIGOLD and MitoCIAO, two searchable compendia to visualize and functionalize protein complexes during mitochondrial remodeling
Year: 2025
Type: article
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 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.
Source: Cell Metabolism
Authors: Giovanni Rigoni, Enrique Calvo, Christina Glytsou, Marta Carro-Alvarellos, Masafumi Noguchi, Martina Semenzato, Charlotte Quirin, Federico Caicci, Natascia Meneghetti, Mattia Sturlese, Takaya Ishihara, Stefano Moro, Chiara Rampazzo, Naotada Ishihara, Fabrizio Bezzo, Leonardo Salviati, Jesùs Vazquez, Gabriele Sales, Chiara Romualdi, Jose Antonio Enriquez, Luca Scorrano, Maria Eugenia Soriano
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: Fondazione Città della Speranza, Fondazione Cassa di Risparmio di Padova e Rovigo, Japan Agency for Medical Research and Development, “la Caixa” Foundation, Ministerio de Ciencia, Innovación y Universidades, Japan Society for the Promotion of Science London, European Commission, Fondazione Telethon, Ministero dell’Istruzione, dell’Università e della Ricerca, Università degli Studi di Padova, Associazione Italiana per la Ricerca sul Cancro, Ministero dell'Università e della Ricerca, Japan Society for the Promotion of Science, Instituto de Salud Carlos III, European Regional Development Fund, Core Research for Evolutional Science and Technology, FP7 Ideas: European Research Council
Awards: ミトコンドリア核様体ダイナミクスの基本原理の理解と生理・病態における意義の解明, G1198753641, G1893433196, G2140656191, G2643629490, G287067328, G41939404, G4545431484, G5925296822, G6731467812, G6745261595, G7621084294, G7701185710, G7834595851, 気道上皮基底幹細胞の制御とその破綻におけるミトコンドリア内膜因子OPA1の役割の解明, G8520508164, Extending the Optic atrophy 1 dependent cristae remodeling: from models to a rationale for therapy of autosomal dominant optic atrophy
OpenAlex ID: W4407904584