美国陈-扎克伯格生物中心Manuel D. Leonetti等研究人员合作发现，全局细胞器谱分析揭示了亚细胞定位和蛋白质组尺度上的重塑。这一研究成果于2024年12月31日在线发表在国际学术期刊《细胞》上。
研究人员提出了一种高分辨率策略，通过将细胞器免疫捕获与质谱联用，绘制亚细胞组织图谱。研究人员将这一工作流程应用于细胞内膜性和无膜区室的全面收集。基于图形分析，研究人员为超过7600种蛋白质分配了亚细胞定位，定义了空间网络，并揭示了细胞区室之间的相互连接。
该方法可以用于全面分析细胞扰动过程中蛋白质组的重塑。通过表征HCoV-OC43病毒感染后的细胞景观，研究人员发现许多蛋白质的调控是通过其空间分布的变化，而非丰度的变化来实现的。
结果表明，蛋白质组范围的亚细胞重塑分析为阐明细胞响应提供了关键见解，并揭示了铁死亡在OC43感染中的重要作用。这些数据集可以通过organelles.czbiohub.org进行探索。
据悉，定义所有人类蛋白质的亚细胞分布，及其在细胞状态变化中的重塑，仍然是细胞生物学中的核心目标。
附：英文原文
Title: Global organelle profiling reveals subcellular localization and remodeling at proteome scale
Author: Marco Y. Hein, Duo Peng, Verina Todorova, Frank McCarthy, Kibeom Kim, Chad Liu, Laura Savy, Camille Januel, Rodrigo Baltazar-Nunez, Madhurya Sekhar, Shivanshi Vaid, Sophie Bax, Madhuri Vangipuram, James Burgess, Leila Njoya, Eileen Wang, Ivan E. Ivanov, Janie R. Byrum, Soorya Pradeep, Carlos G. Gonzalez, Yttria Aniseia, Joseph S. Creery, Aidan H. McMorrow, Sara Sunshine, Serena Yeung-Levy, Brian C. DeFelice, Shalin B. Mehta, Daniel N. Itzhak, Joshua E. Elias, Manuel D. Leonetti
Issue&Volume: 2024-12-31
Abstract: Defining the subcellular distribution of all human proteins and their remodeling across cellular states remains a central goal in cell biology. Here, we present a high-resolution strategy to map subcellular organization using organelle immunocapture coupled to mass spectrometry. We apply this workflow to a cell-wide collection of membranous and membraneless compartments. A graph-based analysis assigns the subcellular localization of over 7,600 proteins, defines spatial networks, and uncovers interconnections between cellular compartments. Our approach can be deployed to comprehensively profile proteome remodeling during cellular perturbation. By characterizing the cellular landscape following HCoV-OC43 viral infection, we discover that many proteins are regulated by changes in their spatial distribution rather than by changes in abundance. Our results establish that proteome-wide analysis of subcellular remodeling provides key insights for elucidating cellular responses, uncovering an essential role for ferroptosis in OC43 infection. Our dataset can be explored at organelles.czbiohub.org.
DOI: 10.1016/j.cell.2024.11.028
Source: https://www.cell.com/cell/abstract/S0092-8674(24)01344-8