{"entity": "researcher", "timestamp": "2026-08-20T21:19:52.963Z", "family": "Shoaib", "given": "Muhammad", "initials": "M", "orcid": "0000-0003-1296-5005", "affiliations": ["Biotech Research and Innovation Centre (BRIC), University of Copenhagen, DK-2200 Copenhagen, Denmark."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/a90b52fbd71d432982b9807804e881f2.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/a90b52fbd71d432982b9807804e881f2"}}, "publications": [{"entity": "publication", "iuid": "7d790256dedb49e79dd2a8f355a9f954", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/7d790256dedb49e79dd2a8f355a9f954.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/7d790256dedb49e79dd2a8f355a9f954"}}, "title": "Lamin A/C impairments cause mitochondrial dysfunction by attenuating PGC1\u03b1 and the NAMPT-NAD+ pathway.", "authors": [{"family": "Maynard", "given": "Scott", "initials": "S", "orcid": "0000-0001-5625-936X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/608188a808184753bc3ed43e2911154c.json"}}, {"family": "Hall", "given": "Arnaldur", "initials": "A"}, {"family": "Galanos", "given": "Panagiotis", "initials": "P", "orcid": "0000-0003-1403-4685", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9d1071fd28cb42d6b328182cddfd341f.json"}}, {"family": "Rizza", "given": "Salvatore", "initials": "S"}, {"family": "Yamamoto", "given": "Tatsuro", "initials": "T"}, {"family": "Gram", "given": "Helena Hagner", "initials": "HH"}, {"family": "Munk", "given": "Sebastian H N", "initials": "SHN"}, {"family": "Shoaib", "given": "Muhammad", "initials": "M", "orcid": "0000-0003-1296-5005", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a90b52fbd71d432982b9807804e881f2.json"}}, {"family": "S\u00f8rensen", "given": "Claus Storgaard", "initials": "CS"}, {"family": "Bohr", "given": "Vilhelm A", "initials": "VA", "orcid": "0000-0003-4823-6429", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/57e81811b78745cc842862146c6ee7b2.json"}}, {"family": "Lerdrup", "given": "Mads", "initials": "M"}, {"family": "Maya-Mendoza", "given": "Apolinar", "initials": "A"}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/288939950c0c4c6393d35c84e5128b5f.json"}}], "type": "journal article", "published": "2022-09-23", "journal": {"title": "Nucleic Acids Res.", "issn": "1362-4962", "volume": "50", "issue": "17", "pages": "9948-9965", "issn-l": "0305-1048"}, "abstract": "Mutations in the lamin A/C gene (LMNA) cause laminopathies such as the premature aging Hutchinson Gilford progeria syndrome (HGPS) and altered lamin A/C levels are found in diverse malignancies. The underlying lamin-associated mechanisms remain poorly understood. Here we report that lamin A/C-null mouse embryo fibroblasts (Lmna-/- MEFs) and human progerin-expressing HGPS fibroblasts both display reduced NAD+ levels, unstable mitochondrial DNA and attenuated bioenergetics. This mitochondrial dysfunction is associated with reduced chromatin recruitment (Lmna-/- MEFs) or low levels (HGPS) of PGC1\u03b1, the key transcription factor for mitochondrial homeostasis. Lmna-/- MEFs showed reduced expression of the NAD+-biosynthesis enzyme NAMPT and attenuated activity of the NAD+-dependent deacetylase SIRT1. We find high PARylation in lamin A/C-aberrant cells, further decreasing the NAD+ pool and consistent with impaired DNA base excision repair in both cell models, a condition that fuels DNA damage-induced PARylation under oxidative stress. Further, ATAC-sequencing revealed a substantially altered chromatin landscape in Lmna-/- MEFs, including aberrantly reduced accessibility at the Nampt gene promoter. Thus, we identified a new role of lamin A/C as a key modulator of mitochondrial function through impairments of PGC1\u03b1 and the NAMPT-NAD+ pathway, with broader implications for the aging process.", "doi": "10.1093/nar/gkac741", "pmid": "36099415", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9508839"}, {"db": "pii", "key": "6696852"}], "notes": [], "created": "2026-08-20T09:49:53.952Z", "modified": "2026-08-20T09:49:54.099Z"}]}