Global organelle profiling reveals subcellular localization and remodeling at proteome scale
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.
Authors
- Marco Y. Hein (ORCID: https://orcid.org/0000-0002-9490-2261)
- Aidan H. McMorrow (ORCID: https://orcid.org/0000-0003-3781-9354)
- Joshua Eric Elias (ORCID: https://orcid.org/0000-0002-8063-3259)
- Shalin B. Mehta (ORCID: https://orcid.org/0000-0002-2542-3582)
- Chad Liu (ORCID: https://orcid.org/0000-0002-8345-8847)
- Brian C. DeFelice (ORCID: https://orcid.org/0000-0001-8243-0300)
- Frank M. McCarthy (ORCID: https://orcid.org/0000-0002-7933-6847)
- Kibeom Kim (ORCID: https://orcid.org/0000-0002-0764-4875)
- Manuel D. Leonetti (ORCID: https://orcid.org/0000-0002-4881-405X)
- Janie R. Byrum (ORCID: https://orcid.org/0000-0003-0828-5074)
- Shivanshi Vaid (ORCID: https://orcid.org/0009-0006-2481-4609)
- Laura Savy
- Madhuri Vangipuram (ORCID: https://orcid.org/0000-0001-7271-2689)
- Joseph S. Creery (ORCID: https://orcid.org/0000-0003-4029-2784)
- Verina Todorova (ORCID: https://orcid.org/0000-0002-3776-4253)
- Eileen Wang (ORCID: https://orcid.org/0000-0002-3149-3229)
- Sara Sunshine (ORCID: https://orcid.org/0000-0002-1897-5063)
- Sonal Sekhar Miraj (ORCID: https://orcid.org/0000-0003-3660-2022)
- Sophie Bax (ORCID: https://orcid.org/0009-0001-7820-2716)
- James Burgess (ORCID: https://orcid.org/0000-0002-0823-2848)
- Camille Januel
- Ivan E. Ivanov (ORCID: https://orcid.org/0000-0001-6389-0213)
- Duo Peng (ORCID: https://orcid.org/0000-0001-7540-8623)
- Soorya Pradeep (ORCID: https://orcid.org/0000-0002-0926-1480)
- Daniel N. Itzhak (ORCID: https://orcid.org/0000-0002-4720-273X)
- Carlos G. Gonzalez (ORCID: https://orcid.org/0000-0002-4673-4048)
- Serena Yeung-Levy
- Yttria Aniseia
- Rodrigo Baltazar-Nunez
- Leila Njoya
Institutions
- University of California, San Francisco (US)
- Chan Zuckerberg Initiative (United States) (US)
- Stanford University (US)
Publication Details
- Journal
- Cell
- Published
- 2024-12-31
- DOI
- https://doi.org/10.1016/j.cell.2024.11.028
- Citations
- 62
- Primary Topic
- Advanced Proteomics Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 14.93