Cell Metab. 2025 Feb 20. pii: S1550-4131(25)00017-8. [Epub ahead of print]
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.
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.
Keywords: ATAD3A; OPA1; cristae remodeling; interactome; mitochondria; mitochondrial complexes; mitoribosome stability