Distinct roles of COPI proteins attenuated in cell senescence
In senescent cells, functional alterations in organelles like mitochondria and lysosomes are well characterized, but senescence-associated changes in Golgi function are not. An RNA interference screen revealed that silencing subunits of the coatomer protein I (COPI) complex, critical for intracellular transport involving the Golgi, reduced extracellular vesicle uptake. In proliferating WI-38 fibroblasts, silencing COPI constituents COPA, COPB1, COPB2, or COPD induced ATF4 production and disrupted autophagy, apoptosis, and cytokine signaling, all hallmarks of impaired Golgi-to-endoplasmic reticulum transport, while silencing COPI constituents COPG1, COPE, or COPZ1 altered the production of extracellular matrix proteins. Furthermore, individual COPI proteins associated with Golgi and endosomal proteins, supporting roles in vesicular trafficking. In senescent WI-38 fibroblasts, silencing COPI proteins did not elicit these phenotypes. Our findings underscore the distinct, multifunctional actions of individual COPI proteins and their key roles in intracellular homeostatic transport networks that become attenuated during senescence.
Authors
- Jennifer L. Martindale (ORCID: https://orcid.org/0000-0002-3234-6861)
- Martín Salamini-Montemurri (ORCID: https://orcid.org/0000-0002-0149-5493)
- Qiong Meng (ORCID: https://orcid.org/0000-0002-2498-9816)
- Supriyo De (ORCID: https://orcid.org/0000-0002-2075-7655)
- Myriam Gorospe (ORCID: https://orcid.org/0000-0001-5439-3434)
- Martina Rossi (ORCID: https://orcid.org/0000-0001-7738-9841)
- Apala Pal (ORCID: https://orcid.org/0000-0003-4668-6434)
- Sarah Buchman
- Dimitrios Tsitsipatis
- Krystyna Mazan-Mamczarz (ORCID: https://orcid.org/0009-0005-1545-0500)
- Marika Oksanen (ORCID: https://orcid.org/0000-0003-4140-4282)
- Allison B. Herman (ORCID: https://orcid.org/0000-0003-3826-3247)
- Kyoung Mi Kim (ORCID: https://orcid.org/0000-0002-2845-5678)
- Chang Hoon Shin
- Jinshui Fan (ORCID: https://orcid.org/0009-0001-9300-1920)
- Yulan Piao
- Eleanor J. Wind
- Jixiang Leng (ORCID: https://orcid.org/0009-0002-2980-0055)
- Rachel Munk
- Braden Daugherty (ORCID: https://orcid.org/0009-0002-5568-2718)
Institutions
- Chungnam National University (KR)
- Institute on Aging (US)
- National Institute on Aging (US)
Publication Details
- Journal
- Science Advances
- Published
- 2026-07-23
- DOI
- https://doi.org/10.1126/sciadv.aec2786
- Primary Topic
- Cellular transport and secretion
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Research Foundation of Korea