{"entity": "publication", "iuid": "cba67b05ce7f4cd2a8af7b6871e6ccb6", "timestamp": "2026-08-20T21:18:38.726Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/cba67b05ce7f4cd2a8af7b6871e6ccb6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/cba67b05ce7f4cd2a8af7b6871e6ccb6"}}, "title": "Cyclophilin D plays a critical role in the survival of senescent cells.", "authors": [{"family": "Protasoni", "given": "Margherita", "initials": "M"}, {"family": "L\u00f3pez-Polo", "given": "Vanessa", "initials": "V", "orcid": "0000-0001-6165-2510", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6533bccc17664cbe837a56914580d01d.json"}}, {"family": "Stephan-Otto Attolini", "given": "Camille", "initials": "C"}, {"family": "Brandariz", "given": "Julian", "initials": "J", "orcid": "0009-0006-4316-3952", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a03eedc015b64e51bf686044c658b319.json"}}, {"family": "Herranz", "given": "Nicolas", "initials": "N"}, {"family": "Mateo", "given": "Joaquin", "initials": "J"}, {"family": "Ruiz", "given": "Sergio", "initials": "S", "orcid": "0000-0002-0177-6965", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a1df9c89b653456fbcb710b8e749f346.json"}}, {"family": "Fernandez-Capetillo", "given": "Oscar", "initials": "O", "orcid": "0000-0002-2690-6885", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ab1f07900e6e466d83763e5fe0020ed6.json"}}, {"family": "Kovatcheva", "given": "Marta", "initials": "M", "orcid": "0000-0002-2536-1043", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c04ebf2b2e9c4577bf12a901f57b1c06.json"}}, {"family": "Serrano", "given": "Manuel", "initials": "M", "orcid": "0000-0001-7177-9312", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/26e4038046f3446ebcb124419692eed4.json"}}], "type": "journal article", "published": "2024-12-00", "journal": {"title": "EMBO J.", "issn": "1460-2075", "volume": "43", "issue": "23", "pages": "5972-6000", "issn-l": "0261-4189"}, "abstract": "Senescent cells play a causative role in many diseases, and their elimination is a promising therapeutic strategy. Here, through a genome-wide CRISPR/Cas9 screen, we identify the gene PPIF, encoding the mitochondrial protein cyclophilin D (CypD), as a novel senolytic target. Cyclophilin D promotes the transient opening of the mitochondrial permeability transition pore (mPTP), which serves as a failsafe mechanism for calcium efflux. We show that senescent cells exhibit a high frequency of transient CypD/mPTP opening events, known as 'flickering'. Inhibition of CypD using genetic or pharmacologic tools, including cyclosporin A, leads to the toxic accumulation of mitochondrial Ca2+ and the death of senescent cells. Genetic or pharmacological inhibition of NCLX, another mitochondrial calcium efflux channel, also leads to senolysis, while inhibition of the main Ca2+ influx channel, MCU, prevents senolysis induced by CypD inhibition. We conclude that senescent cells are highly vulnerable to elevated mitochondrial Ca2+ ions, and that transient CypD/mPTP opening is a critical adaptation mechanism for the survival of senescent cells.", "doi": "10.1038/s44318-024-00259-2", "pmid": "39448884", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11612481"}, {"db": "pii", "key": "10.1038/s44318-024-00259-2"}], "notes": [], "created": "2026-08-20T09:26:41.098Z", "modified": "2026-08-20T09:26:41.345Z"}