2025年2月24日，帕多瓦大学Maria Eugenia Soriano研究团队在《细胞—代谢》杂志发表论文，他们的研究开发出了MARIGOLD和MitoCIAO，在线粒体重塑过程中可视化和功能化蛋白质复合物的两个可搜索的纲要。

课题组生成并验证了这些线粒体复合物的两个可搜索的概要。通过质谱鉴定，从未受干扰的、冠状重构的和外膜通透化的线粒体中分离出蓝色天然凝胶电泳的复合物中的蛋白质，该团队创建了MARIGOLD，一个包含627种蛋白质的线粒体凋亡重构复合物数据库。MARIGOLD阐明了在线粒体膜重塑过程中蛋白质在复合体中的动态分布。从MARIGOLD，研究小组开发了MitoCIAO，一个线粒体复合体相互作用组工具，通过统计相关性，计算复合体中蛋白质共发生的可能性。MitoCIAO正确预测了线粒体嵴组织系统（MICOS）和视神经萎缩1 （OPA1）复合物组分之间经过生物学验证的相互作用。研究团队利用MitoCIAO实现了两种ATP酶家族AAA结构域3A （ATAD3A）复合物的功能化：一种含有调节线粒体超微结构的OPA1，另一种含有对线粒体稳定性至关重要的核糖体蛋白。这些纲要揭示了线粒体复合物的动态性质，并使其功能化。

据介绍，线粒体蛋白动态组装在高分子量复合物中，对其功能至关重要。

附：英文原文

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

Author: 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

Issue&Volume: 2025-02-24

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.

DOI: 10.1016/j.cmet.2025.01.017

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00017-8