{"entity": "researcher", "timestamp": "2026-06-15T08:38:16.556Z", "family": "Zuppardo", "given": "Alessandro", "initials": "A", "orcid": "0000-0001-9601-3567", "affiliations": ["Veneto Institute of Molecular Medicine (VIMM), Via Orus, 2-35129, Padova, Italy.", "Department of Biomedical Sciences, University of Padova, Via Ugo Bassi, 58/B-35131, Padova, Italy."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/308877ae9bac46328666ca4e56b73d26.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/308877ae9bac46328666ca4e56b73d26"}}, "publications": [{"entity": "publication", "iuid": "499254acb4eb4139bf11f17fd8968652", "links": {"self": {"href": "https://publications.scilifelab.se/publication/499254acb4eb4139bf11f17fd8968652.json"}, "display": {"href": "https://publications.scilifelab.se/publication/499254acb4eb4139bf11f17fd8968652"}}, "title": "Modelling POLG mutations in mice unravels a critical role of POL\u03b3\u0392 in regulating phenotypic severity.", "authors": [{"family": "Corr\u00e0", "given": "Samantha", "initials": "S"}, {"family": "Zuppardo", "given": "Alessandro", "initials": "A", "orcid": "0000-0001-9601-3567", "researcher": {"href": "https://publications.scilifelab.se/researcher/308877ae9bac46328666ca4e56b73d26.json"}}, {"family": "Valenzuela", "given": "Sebastian", "initials": "S", "orcid": "0000-0001-5153-8431", "researcher": {"href": "https://publications.scilifelab.se/researcher/16c5cd1a4e8a4d9389514f33049240a5.json"}}, {"family": "Jenninger", "given": "Louise", "initials": "L"}, {"family": "Cerutti", "given": "Raffaele", "initials": "R"}, {"family": "Sillamaa", "given": "Sirelin", "initials": "S", "orcid": "0000-0001-8077-9963", "researcher": {"href": "https://publications.scilifelab.se/researcher/29a3fbab3f684386a2e08236bfd8674e.json"}}, {"family": "Hoberg", "given": "Emily", "initials": "E"}, {"family": "Johansson", "given": "Katarina A S", "initials": "KAS", "orcid": "0009-0005-8992-7631", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3bac3ed243c4f0493e0d494f79a7ca2.json"}}, {"family": "Rovsnik", "given": "Urska", "initials": "U"}, {"family": "Volta", "given": "Sara", "initials": "S"}, {"family": "Silva-Pinheiro", "given": "Pedro", "initials": "P", "orcid": "0000-0002-0872-5749", "researcher": {"href": "https://publications.scilifelab.se/researcher/bbc93779b0704e55a91eb4d755255aed.json"}}, {"family": "Davis", "given": "Hannah", "initials": "H"}, {"family": "Trifunovic", "given": "Aleksandra", "initials": "A", "orcid": "0000-0002-5472-3517", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf7d2fa56e714134bc66ca5884b8e86b.json"}}, {"family": "Minczuk", "given": "Michal", "initials": "M", "orcid": "0000-0001-8242-1420", "researcher": {"href": "https://publications.scilifelab.se/researcher/8f03f6f8725149c6938067d043ca4f7f.json"}}, {"family": "Gustafsson", "given": "Claes M", "initials": "CM", "orcid": "0000-0003-3531-8468", "researcher": {"href": "https://publications.scilifelab.se/researcher/2851656430d147dab7a8a32e50fee7b7.json"}}, {"family": "Suomalainen", "given": "Anu", "initials": "A", "orcid": "0000-0003-4833-5195", "researcher": {"href": "https://publications.scilifelab.se/researcher/6625705a6d4246c3a5f397008173899f.json"}}, {"family": "Zeviani", "given": "Massimo", "initials": "M"}, {"family": "Macao", "given": "Bertil", "initials": "B", "orcid": "0000-0001-6511-6125", "researcher": {"href": "https://publications.scilifelab.se/researcher/b5445196c3234bdb8686e85f77a66f3f.json"}}, {"family": "Zhu", "given": "Xuefeng", "initials": "X", "orcid": "0000-0002-4759-4446", "researcher": {"href": "https://publications.scilifelab.se/researcher/eebd5f32ac0c48869c90ba2d2ba94fa9.json"}}, {"family": "Falkenberg", "given": "Maria", "initials": "M", "orcid": "0000-0001-8713-173X", "researcher": {"href": "https://publications.scilifelab.se/researcher/562109b99a5c4eb3bd8b92f30014828b.json"}}, {"family": "Viscomi", "given": "Carlo", "initials": "C", "orcid": "0000-0001-6050-0566", "researcher": {"href": "https://publications.scilifelab.se/researcher/e84ba370ae594e6db85d338ab69a02df.json"}}], "type": "journal article", "published": "2025-05-23", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "16", "issue": "1", "pages": "4782", "issn-l": "2041-1723"}, "abstract": "DNA polymerase \u03b3 (POL\u03b3), responsible for mitochondrial DNA replication, consists of a catalytic POL\u03b3A subunit and two accessory POL\u03b3B subunits. Mutations in POLG, which encodes POL\u03b3A, lead to various mitochondrial diseases. We investigated the most common POLG mutations (A467T, W748S, G848S, Y955C) by characterizing human and mouse POL\u03b3 variants. Our data reveal that these mutations significantly impair POL\u03b3 activities, with mouse variants exhibiting milder defects. Cryogenic electron microscopy highlighted structural differences between human and mouse POL\u03b3, particularly in the POL\u03b3B subunit, which may explain the higher activity of mouse POL\u03b3 and the reduced severity of mutations in mice. We further generated a panel of mouse models mirroring common human POLG mutations, providing crucial insights into the pathogenesis of POLG-related disorders and establishing robust models for therapeutic development. Our findings emphasize the importance of POL\u03b3B in modulating the severity of POLG mutations.", "doi": "10.1038/s41467-025-60059-y", "pmid": "40404629", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12098916"}, {"db": "pii", "key": "10.1038/s41467-025-60059-y"}], "notes": [], "created": "2025-11-05T13:48:13.014Z", "modified": "2025-11-13T12:47:34.901Z"}]}