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We have identified a novel function of the p53 family protein TAp73 in regulating mitochondrial dynamics. TAp73 regulates the expression of Optic Atrophy 1 (OPA1), a protein responsible for controlling mitochondrial fusion, cristae biogenesis and electron transport chain function. Disruption of this axis results in a fragmented mitochondrial network and an impaired capacity for energy production\n                    <jats:italic>via<\/jats:italic>\n                    oxidative phosphorylation. Owing to the role of OPA1 in modulating cytochrome\n                    <jats:italic>c<\/jats:italic>\n                    release, TAp73\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    cells display an increased sensitivity to apoptotic cell death, e.g.,\n                    <jats:italic>via<\/jats:italic>\n                    BH3-mimetics. We additionally show that the TAp73\/OPA1 axis has functional relevance in the upper airway, where TAp73 expression is essential for multiciliated cell differentiation and function. Consistently, ciliated epithelial cells of\n                    <jats:italic>Trp73<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    (global p73 knock-out) mice display decreased expression of OPA1 and perturbations of the mitochondrial network, which may drive multiciliated cell loss. In support of this,\n                    <jats:italic>Trp73<\/jats:italic>\n                    and\n                    <jats:italic>OPA1<\/jats:italic>\n                    gene expression is decreased in chronic obstructive pulmonary disease (COPD) patients, a disease characterised by alterations in mitochondrial dynamics. We therefore highlight a potential mechanism involving the loss of p73 in COPD pathogenesis. Our findings also add to the growing body of evidence for growth-promoting roles of TAp73 isoforms.\n                  <\/jats:p>","DOI":"10.1038\/s41419-024-07130-6","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T16:11:35Z","timestamp":1731082295000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["TAp73 regulates mitochondrial dynamics and multiciliated cell homeostasis through an OPA1 axis"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3676-0741","authenticated-orcid":false,"given":"Niall A.","family":"Buckley","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Craxton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Ming","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8723-9564","authenticated-orcid":false,"given":"Emanuele","family":"Panatta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia Giraldez","family":"Pinon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sina","family":"Beier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lajos","family":"Kalmar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaime","family":"Llodr\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuhiro","family":"Morone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9126-5391","authenticated-orcid":false,"given":"Ivano","family":"Amelio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9428-5972","authenticated-orcid":false,"given":"Gerry","family":"Melino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. 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